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Alpha-synuclein is a protein that is abundant in the human brain.[4] Smaller amounts are found in the heart, muscles, and other tissues.[4] In the brain, alpha-synuclein is found mainly at the tips of nerve cells (neurons) in specialized structures called presynaptic terminals.[4] Within these structures, alpha-synuclein interacts withphospholipids[5] and proteins.[4]Presynaptic terminals release chemical messengers, called neurotransmitters, from compartments known as synaptic vesicles. The release of neurotransmitters relays signals between neurons and is critical for normal brain function.[4]
Although the function of alpha-synuclein is not well understood, studies suggest that it plays a role in maintaining a supply of synaptic vesicles in presynaptic terminals by clustering synaptic vesicles.[6] It may also help regulate the release of dopamine, a type of neurotransmitter that is critical for controlling the start and stop of voluntary and involuntary movements.[4]
The human alpha-synuclein protein is made of 140 amino acids and is encoded by the SNCA gene.[7][8][9] An alpha-synuclein fragment, known as the non-Abeta component (NAC) ofAlzheimer's disease amyloid, originally found in an amyloid-enriched fraction, was shown to be a fragment of its precursor protein, NACP.[7] It was later determined that NACP was the human homologue of Torpedo synuclein. Therefore, NACP is now referred to as human alpha-synuclein.



Tissue expression[edit]

Alpha-synuclein is a synuclein protein of unknown function primarily found in neural tissue, making up as much as 1% of all proteins in the cytosol of brain cells.[10] It is predominantly expressed in the neocortex, hippocampus, substantia nigra, thalamus, and cerebellum. It is predominantly a neuronal protein, but can also be found in the neuroglial cells.[citation needed] In melanocytic cells, SNCA protein expression may be regulated by MITF.[11]
It has been established that alpha-synuclein is extensively localized in the nucleus of mammalian brain neurons, suggesting a role of alpha-synuclein in the nucleus.[12] Synuclein is however found predominantly in the presynaptic termini, in both free or membrane-bound forms,[13] with roughly 15% of synuclein being membrane-bound in any moment in neurons.[14]
Recently, it has been shown that alpha-synuclein is localized in neuronal mitochondria.[15][16]Alpha-synuclein is highly expressed in the mitochondria in olfactory bulb, hippocampus, striatum and thalamus, where the cytosolic alpha-synuclein is also rich. However, the cerebral cortex and cerebellum are two exceptions, which contain rich cytosolic alpha-synuclein but very low levels of mitochondrial alpha-synuclein. It has been shown that alpha-synuclein is localized in the inner membrane of mitochondria, and that the inhibitory effect of alpha-synuclein on complex I activity of mitochondrial respiratory chain is dose-dependent. Thus, it is suggested that alpha-synuclein in mitochondria is differentially expressed in different brain regions and the background levels of mitochondrial alpha-synuclein may be a potential factor affecting mitochondrial function and predisposing some neurons to degeneration.[16]
At least three isoforms of synuclein are produced through alternative splicing.[17] The majority form of the protein, and the one most investigated, is the full-length protein of 140 amino acids. Other isoforms are alpha-synuclein-126, which lacks residues 41-54 due to loss of exon 3; and alpha-synuclein-112,[18] which lacks residue 103-130 due to loss of exon 5.[17]


Alpha-synuclein in solution is considered to be an intrinsically disordered protein, i.e. it lacks a single stable 3D structure.[19] As of 2014, an increasing number of reports suggest, however, the presence of partial structures or mostly structured oligomeric states in the solution structure of alpha-synuclein even in the absence of lipids. This trend is also supported by a large number of single molecule (optical tweezers) measurements on single copies of monomeric alpha-synuclein as well as covalently enforced dimers or tetramers of alpha-synuclein.[20]


Alpha-synuclein is specifically upregulated in a discrete population of presynaptic terminals of the brain during a period of acquisition-related synaptic rearrangement.[21] It has been shown that alpha-synuclein significantly interacts with tubulin,[22] and that alpha-synuclein may have activity as a potential microtubule-associated protein, like tau.[23]
Recent evidence suggests that alpha-synuclein functions as a molecular chaperone in the formation of SNARE complexes.[24][25] In particular, it simultaneously binds to phospholipids of the plasma membrane via its N-terminus domain and to synaptobrevin-2 via its C-terminus domain, with increased importance during synaptic activity.[26] Indeed, there is growing evidence that alpha-synuclein is involved in the functioning of the neuronal Golgi apparatus and vesicletrafficking.[27]
Apparently, alpha-synuclein is essential for normal development of the cognitive functions. Knock-out mice with the targeted inactivation of the expression of alpha-synuclein show impaired spatial learning and working memory.[28]

Interaction with lipid membranes[edit]

Experimental evidence has been collected on the interaction of alpha-synuclein with membraneand its involvement with membrane composition and turnover. Yeast genome screening has found that several genes that deal with lipid metabolism play a role in alpha-synuclein toxicity.[29]Conversely, alpha-synuclein expression levels can affect the viscosity and the relative amount of fatty acids in the lipid bilayer.[30]
Alpha-synuclein is known to directly bind to lipid membranes, associating with the negatively charged surfaces of phospholipids.[30] Alpha-synuclein forms an extended helical structure on small unilamellar vesicles.[31] A preferential binding to small vesicles has been found.[32] The binding of alpha-synuclein to lipid membranes has complex effects on the latter, altering the bilayer structure and leading to the formation of small vesicles.[33] Alpha-synuclein has been shown to bend membranes of negatively charged phospholipid vesicles and form tubules from large lipid vesicles.[34] Using cryo-EM it was shown that these are micellar tubes of ~5-6 nm diameter.[35] Alpha-synuclein has also been shown to form lipid disc-like particles similar toapolipoproteins [1].[36] Studies have also suggested a possible antioxidant activity of alpha-synuclein in the membrane.[37]
external image 220px-Lewy_bodies_%28alpha_synuclein_inclusions%29.svg.png

Photomicrographs of regions of substantia nigra in a patient showing Lewy bodies and Lewy neurites in various magnifications


Alpha-synuclein primary structure is usually divided in three distinct domains:

  • Residues 1-60: An amphipathic N-terminal region dominated by four 11-residue repeats including theconsensus sequence KTKEGV. This sequence has a structural alpha helix propensity similar to apolipoproteins-binding domains[38]
  • Residues 61-95: A central hydrophobic region which includes the non-amyloid-β component (NAC) region, involved in protein aggregation[7]
  • Residues 96-140: a highly acidic and proline-rich region which has no distinct structural propensity

Autoproteolytic activity[edit]

The use of high-resolution ion-mobility mass spectrometry (IMS-MS) on HPLC-purified alpha-synuclein in vitro has shown alpha-synuclein to be autoproteolytic (self-proteolytic), generating a variety of small molecular weight fragments upon incubation.[39] The 14.46 kDa protein was found to generate numerous smaller fragments, including 12.16 kDa (amino acids 14-133) and 10.44 kDa (40-140) fragments formed through C- and N-terminal truncation and a 7.27 kDa C-terminal fragment (72-140). The 7.27 kDa fragment, which contains the majority of the NAC region, aggregated considerably faster than full-length alpha-synuclein. It is possible that these autoproteolytic products play a role as intermediates or cofactors in the aggregation of alpha-synuclein in vivo.

Clinical significance[edit]

external image 220px-Lewy_Body_alphaSynuclein.jpg

Positive α-Synuclein staining of aLewy body from a patient who had Parkinson's disease.
Classically considered an unstructured soluble protein, unmutated α-synuclein forms a stably folded tetramerthat resists aggregation.[40] This observation, though reproduced and extended by several labs,[41][42][43] is still a matter of debate in the field due to conflicting reports.[44][45][46] Nevertheless, alpha-synuclein aggregates to form insoluble fibrils in pathological conditions characterized by Lewy bodies, such asParkinson's disease, dementia with Lewy bodies andmultiple system atrophy.[47][48] These disorders are known as synucleinopathies. Alpha-synuclein is the primary structural component of Lewy body fibrils. Occasionally, Lewy bodies contain tau protein;[49]however, alpha-synuclein and tau constitute two distinctive subsets of filaments in the same inclusion bodies.[50] Alpha-synuclein pathology is also found in both sporadic and familial cases with Alzheimer's disease.[51]
The aggregation mechanism of alpha-synuclein is uncertain. There is evidence of a structured intermediate rich in beta structure that can be the precursor of aggregation and, ultimately, Lewy bodies.[52] A single molecule study in 2008 suggests alpha-synuclein exists as a mix of unstructured, alpha-helix, and beta-sheet-rich conformers in equilibrium. Mutations or buffer conditions known to improve aggregation strongly increase the population of the beta conformer, thus suggesting this could be a conformation related to pathogenic aggregation.[53]Among the strategies for treating synucleinopathies are compounds that inhibit aggregation of alpha-synuclein. It has been shown that the small molecule cuminaldehyde inhibits fibrillation of alpha-synuclein.[54] The Epstein-Barr virus has been implicated in these disorders.[55]
In rare cases of familial forms of Parkinson's disease, there is a mutation in the gene coding for alpha-synuclein. Five point mutations have been identified thus far: A53T,[56] A30P,[57] E46K,[58]H50Q,[59] and G51D.[60] It has been reported that some mutations influence the initiation and amplification steps of the aggregation process.[61] Genomic duplication and triplication of the gene appear to be a rare cause of Parkinson's disease in other lineages, although more common than point mutations.[62] Hence certain mutations of alpha-synuclein may cause it to form amyloid-like fibrils that contribute to Parkinson's disease.
Certain sections of the alpha-synuclein protein may play a role in the tauopathies.[63]
A prion form of the protein alpha-synuclein may be a causal agent for the disease multiple system atrophy.[64][65][66]
external image 220px-Events_in_alpha_synuclein_toxicity.jpg

Events in α-synuclein toxicity.[67]
external image 50px-Question_book-new.svg.png
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Antibodies against alpha-synuclein have replaced antibodies against ubiquitin as the gold standard forimmunostaining of Lewy bodies.[68] The central panel in the figure to the right shows the major pathway for protein aggregation. Monomeric α-synuclein is natively unfolded in solution but can also bind to membranes in an α-helical form. It seems likely that these two species exist in equilibrium within the cell, although this is unproven. From in vitro work, it is clear that unfolded monomer can aggregate first into small oligomeric species that can be stabilized by β-sheet-like interactions and then into higher molecular weight insoluble fibrils. In a cellular context, there is some evidence that the presence of lipids can promote oligomer formation: α-synuclein can also form annular, pore-like structures that interact with membranes. The deposition of α-synuclein into pathological structures such as Lewy bodies is probably a late event that occurs in some neurons. On the left hand side are some of the known modifiers of this process. Electrical activity in neurons changes the association of α-synuclein with vesicles and may also stimulate polo-like kinase 2 (PLK2), which has been shown to phosphorylate α-synuclein at Ser129. Other kinases have also been proposed to be involved. As well as phosphorylation, truncation through proteases such as calpains, and nitration, probably through nitric oxide (NO) or other reactive nitrogen species that are present during inflammation, all modify synuclein such that it has a higher tendency to aggregate. The addition of ubiquitin (shown as a black spot) to Lewy bodies is probably a secondary process to deposition. On the right are some of the proposed cellular targets for α-synuclein mediated toxicity, which include (from top to bottom) ER-golgi transport, synaptic vesicles, mitochondria and lysosomes and other proteolytic machinery. In each of these cases, it is proposed that α-synuclein has detrimental effects, listed below each arrow, although at this time it is not clear if any of these are either necessary or sufficient for toxicity in neurons.

Protein-protein interactions[edit]

Alpha-synuclein has been shown to interact with

See also[edit]

  • Synuclein
  • Contursi Terme – the village in Italy where a mutation in the α-synuclein gene led to a family history of Parkinson's disease


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  59. Jump up^ Appel-Cresswell S, Vilarino-Guell C, Encarnacion M, Sherman H, Yu I, Shah B, Weir D, Thompson C, Szu-Tu C, Trinh J, Aasly JO, Rajput A, Rajput AH, Jon Stoessl A, Farrer MJ (Jun 2013). "Alpha-synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease".Movement Disorders. 28 (6): 811–3. doi:10.1002/mds.25421. PMID 23457019.
  60. Jump up^ Lesage S, Anheim M, Letournel F, Bousset L, Honoré A, Rozas N, Pieri L, Madiona K, Dürr A, Melki R, Verny C, Brice A (Apr 2013). "G51D α-synuclein mutation causes a novel parkinsonian-pyramidal syndrome". Annals of Neurology. 73 (4): 459–71. doi:10.1002/ana.23894.PMID 23526723.
  61. Jump up^ Flagmeier, Patrick; Meisl, Georg; Vendruscolo, Michele; Knowles, Tuomas P. J.; Dobson, Christopher M.; Buell, Alexander K.; Galvagnion, Céline (2016-08-29). "Mutations associated with familial Parkinson's disease alter the initiation and amplification steps of α-synuclein aggregation". Proceedings of the National Academy of Sciences: 201604645.doi:10.1073/pnas.1604645113. ISSN 0027-8424. PMID 27573854.
  62. Jump up^ Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, Hulihan M, Peuralinna T, Dutra A, Nussbaum R, Lincoln S, Crawley A, Hanson M, Maraganore D, Adler C, Cookson MR, Muenter M, Baptista M, Miller D, Blancato J, Hardy J, Gwinn-Hardy K (Oct 2003). "alpha-Synuclein locus triplication causes Parkinson's disease". Science. 302 (5646): 841.doi:10.1126/science.1090278. PMID 14593171.
  63. Jump up^ Takeda A, Hashimoto M, Mallory M, Sundsumo M, Hansen L, Masliah E (Mar 2000). "C-terminal alpha-synuclein immunoreactivity in structures other than Lewy bodies in neurodegenerative disorders". Acta Neuropathologica. 99 (3): 296–304.doi:10.1007/PL00007441. PMID 10663973.
  64. Jump up^ Prusiner SB, Woerman AL, Mordes DA, Watts JC, Rampersaud R, Berry DB, Patel S, Oehler A, Lowe JK, Kravitz SN, Geschwind DH, Glidden DV, Halliday GM, Middleton LT, Gentleman SM, Grinberg LT, Giles K (Aug 2015). "Evidence for α-synuclein prions causing multiple system atrophy in humans with parkinsonism". Proceedings of the National Academy of Sciences of the United States of America. 112: E5308–17. doi:10.1073/pnas.1514475112. PMC 4586853Freely accessibleFreely accessible.PMID 26324905.
  65. Jump up^ Weiler N (31 August 2015). "New Type of Prion May Cause, Transmit Neurodegeneration".
  66. Jump up^ Rettner R (31 August 31, 2015). "Another Fatal Brain Disease May Come from the Spread of 'Prion' Proteins". Wired Science. Check date values in: |date= (help)
  67. Jump up^ Cookson MR (2009). "alpha-Synuclein and neuronal cell death". Mol Neurodegener. 4 (1): 9.doi:10.1186/1750-1326-4-9. PMC 2646729Freely accessibleFreely accessible. PMID 19193223.
  68. Jump up^ Fujiwara H, Hasegawa M, Dohmae N, Kawashima A, Masliah E, Goldberg MS, Shen J, Takio K, Iwatsubo T (Feb 2002). "alpha-Synuclein is phosphorylated in synucleinopathy lesions".Nature Cell Biology. 4 (2): 160–4. doi:10.1038/ncb748. PMID 11813001.
  69. Jump up^ Wersinger C, Sidhu A (Apr 2003). "Attenuation of dopamine transporter activity by alpha-synuclein". Neuroscience Letters. 340 (3): 189–92. doi:10.1016/S0304-3940(03)00097-1.PMID 12672538.
  70. Jump up^ Lee FJ, Liu F, Pristupa ZB, Niznik HB (Apr 2001). "Direct binding and functional coupling of alpha-synuclein to the dopamine transporters accelerate dopamine-induced apoptosis". FASEB Journal. 15 (6): 916–26. doi:10.1096/fj.00-0334com. PMID 11292651.
  71. Jump up^ Choi P, Golts N, Snyder H, Chong M, Petrucelli L, Hardy J, Sparkman D, Cochran E, Lee JM, Wolozin B (Sep 2001). "Co-association of parkin and alpha-synuclein". NeuroReport. 12 (13): 2839–43. doi:10.1097/00001756-200109170-00017. PMID 11588587.
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Further reading[edit]

External links[edit]


Alfasynuklein är en form av synuklein, ett protein som finns i nervsystemets vävnad, men som också bygger upp Lewykroppar.

Hos människor kodas alfasynuklein av SNCA-genen.

Dess funktion hos friska personer är okänd,

men det utgör 1 % av cytosolernas proteiner.

Det förekommer i högst grad i neocortex, hippocampus, substantia nigra, talamus och cerebellum.

Framför allt är det ett nervcellsprotein, men det kan finnas i gliaceller.

Det finns också i nervcellernas mitokondrier, framför allt i luktloben, hippocampus, striatumoch talamus, men inte i hjärnbarken eller cerebellum där den bara finns i cytosolen.

Fettomsättningen deltar i toxicitet av alfasynuklein, men alfasynuklein kan påverka viskositeten och den relativa mängden fettsyror i de dubbla lipidlagren.

Normalt är alfasynuklein ett intrinsikalt ostrukturerat protein.

Under vissa patologiska omständigheter kan det också aggregera och bilda olösliga fibriller i hjärnan, som kallas Lewykroppar.

Förekomst av Lewykroppar kallas Lewykroppsjukdom, och kännetecknar Lewykroppsdemens, vissa former av Parkinsons sjukdom och multisystematrofi.

Det förekommer vidare vid vissa former av Alzheimers sjukdom.

Alfasynuklein interagerar normalt med bl.a. dopamintransportproteiner, tau-proteiner, parkin och fosfolipas D1.


α-Synuclein (auch α-Synuklein) ist ein kleines, lösliches Protein im Gehirn von Wirbeltieren,

das unter anderem die Dopamin-Ausschüttung reguliert.

Es ist in der Lage, Membrankanäle zu bilden

und ist daher ein Transportprotein.

Mutationen im SNCAGen sind verantwortlich für Synucleinopathien, wie die erblichen Formen 1 und 4 der Parkinson-Krankheit und der Lewy-Körperchen-Demenz.[2][3][4][5]

Wie der Name impliziert, wurde SNCA initial als synaptisches und nukleäres Protein identifiziert.[6]

Trotz intensiver Studien ist die genaue Rolle von SNCA noch nicht klar definiert:

Es gibt Anzeichen dafür, dass SNCA bei der Aufrechterhaltung des synaptischen Vesikel-Pools eine Rolle spielt
[Aufrechterhaltung = maintaining, preservation, upkeep ]

und die Dopaminfreisetzung moduliert,

aber SNCA-knockout-Mäuse haben keinen offensichtlichen Phänotyp.[7][8]

Die Primärstruktur von α-Synuclein wird in drei verschiedene Domänen unterteilt[9]:


Es wurde im menschlichen Gehirn als Vorstufe des nicht-Amyloid-β-Proteins identifiziert.

Wissenschaftler des US-amerikanischen National Human Genome Research Institute (NHGRI) an den National Institutes of Health (NIH) in Bethesda, Maryland haben 1997 herausgefunden, dass es an mehreren pathogenen Prozessen bei neurodegenerativen Erkrankungen wie zum Beispiel dem Morbus Parkinson beteiligt ist.

So wurde in den für letztere typischen Lewy-Körperchen eine positive Immunreaktion für Antikörper gegen α-Synuclein gefunden.[10]

Diesem Protein wird eine toxische Wirkung auf bestimmte Nervenzellen, vor allem aber auf dopaminerge Neurone der Substantia nigra zugeschrieben, in denen es in Form von Protofibrillen als Mitverursacher oxidativen Stresses und daraus resultierenden neuronalen Zelltodes angesehen wird.[11]

Auch eine Bedeutung der α-Synucleine bei der Entstehung von Prionkrankheiten oder der Alzheimerschen Krankheit wird diskutiert.

Die Gruppe neurodegenerativer Erkrankungen, bei denen es zu einer pathologischen Akkumulation von α-Synuclein im zentralen Nervensystem kommt, bezeichnet man als Synucleinopathien.
Die Wiener Firma AFFiRiS AG führt seit dem 5. Juni 2012 eine klinische Studie mit dem gegen α-Synuclein gerichteten Wirkstoff PD01A durch mit dem Ziel, einen Impfstoff gegen die Parkinsonsche Erkrankung zu entwickeln.
Durch die Impfung soll das Immunsystem angeregt werden, Antikörper gegen α-Synuclein zu bilden.[12][13]

Quellen[Bearbeiten | Quelltext bearbeiten]

  1. Homologe zu P37840 bei OMA
  2. George JM: The synucleins. In: Genome Biol.. 3, Nr. 1, 2002, S. REVIEWS3002. PMID 11806835. PMC 150459 (freier Volltext).
  3. Lavedan C: The synuclein family. In: Genome Res.. 8, Nr. 9, September 1998, S. 871–80. PMID 9750188.doi:10.1101/gr.8.9.871 (zurzeit nicht erreichbar)
  4. UniProt P37840
  5. Pathway DB: //Alpha-synuclein signaling//
  6. L. Maroteaux, J. T. Campanelli, R. H. Scheller: Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. In: The Journal of neuroscience. Band 8, Nummer 8, August 1988, S. 2804–2815, ISSN 0270-6474. PMID 3411354.
  7. A. Abeliovich, Y. Schmitz u. a.: Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. In:Neuron. Band 25, Nummer 1, Januar 2000, S. 239–252, ISSN 0896-6273. PMID 10707987.
  8. D. D. Murphy, S. M. Rueter u. a.: Synucleins are developmentally expressed, and alpha-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons. In: The Journal of neuroscience. Band 20, Nummer 9, Mai 2000, S. 3214–3220, ISSN 1529-2401. PMID 10777786.
  9. L.Breydo, J.W.Wu, A. Uversky: α-Synuclein misfolding and Parkinson's disease In: Biochimica et Biophysica Acta. Band 1822, Nummer 2, Februar 2012, S. 261-285, PMID 22024360.
  10. Brunn, A.: Vorlesung Allgemeine Pathologie. Abteilung für Neuropathologie, Universität zu Köln, Sommersemester 2005. PDF(Memento vom 24. April 2009 im Internet Archive)
  11. Tolnay, M. (2000): α-Synuclein und Tau: abnorme Proteinablagerungen beim Parkinson-(plus)-Syndrom. In: Schweiz. Arch. Neurol. Psychiatr. Bd. 151, S. 136-145. [1]
  12. //Parkinson-Impfstoff – weltweit erste klinische Studie in Wien.// AFFiRiS AG, 5. Juni 2012, abgerufen am 11. Juni 2012.
  13. Thomas H. Maugh: //First trial of vaccine to treat Parkinson's disease begins.// Los Angeles Times, 7. Juni 2012, abgerufen am11. Juni 2012 (englisch).


  • Polymeropoulos MH, Lavedan C, Leroy E, et al.: Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. In:Science. 276, Nr. 5321, Juni 1997, S. 2045–7. doi:10.1126/science.276.5321.2045. PMID 9197268.
  • Neumann M, Kahle PJ, Giasson BI, et al.: Misfolded proteinase K-resistant hyperphosphorylated alpha-synuclein in aged transgenic mice with locomotor deterioration and in human alpha-synucleinopathies. In: J. Clin. Invest.. 110, Nr. 10, November 2002, S. 1429–39.doi:10.1172/JCI15777. PMID 12438441. PMC 151810 (freier Volltext).
  • Sandra Blakeslee: In Folding Proteins, Clues to Many Diseases. In: The New York Times, 21. Mai 2002
  • Jowaed A, Schmitt I, Kaut O, Wüllner U: Methylation regulates alpha-synuclein expression and is decreased in Parkinson's disease patients' brains. In: J. Neurosci.. 30, Nr. 18, Mai 2010, S. 6355–9. doi:10.1523/JNEUROSCI.6119-09.2010. PMID 20445061.
  • K. C. Luk, V. Kehm u. a.: Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice.In: Science. Band 338, Nummer 6109, November 2012, S. 949–953, ISSN 1095-9203. doi:10.1126/science.1227157. PMID 23161999. PMC 3552321 (freier Volltext).


Commons: alpha synuclein – Sammlung von Bildern, Videos und Audiodateien


Parkinson's disease (PD) and related α-synucleinopathies are defined by the accumulation of α-synuclein (α-Syn)–containing intraneuronal inclusions—Lewy bodies (LBs) and Lewy neurites (LNs)—in association with the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and other brain regions.

However, a cause-and-effect relationship between LB/LN formation and neurodegeneration remains unclear.

Indeed, whether LB/LNs are toxic or represent a neuroprotective response has been contentious.

Luk et al. (p. 949) injected α-Syn fibrils generated from recombinant mouse α-Syn protein into the dorsal striatum of wild-type mice and found that misfolded α-Syn caused the formation of PD-like LB/LNs and subsequent cell-to-cell transmission of pathologic α-Syn to anatomically interconnected regions, including the SNpc.

Furthermore, the formation of LB/LNs and their accumulation in SNpc resulted in the progressive loss of these dopaminergic neurons, reduced dopamine innervations to the dorsal striatum, and culminated in motor deficits similar to PD.

Thus, a synthetic misfolded wild-type protein (that is, α-Syn) was able to elicit and transmit disease pathology and neurodegeneration in healthy nontransgenic mice.

Parkinson’s disease is characterized by abundant α-synuclein (α-Syn) neuronal inclusions, known as Lewy bodies and Lewy neurites,

Parkinson’s disease is characterized by
the massive loss of midbrain dopamine neurons.

However, a cause-and-effect relationship between Lewy inclusion formation and neurodegeneration remains unclear.

Here, we found that in wild-type nontransgenic mice, a single intrastriatal inoculation of synthetic α-Syn fibrils led to the cell-to-cell transmission of pathologic α-Syn and Parkinson’s-like Lewy pathology in anatomically interconnected regions.

Lewy pathology accumulation resulted in progressive loss of dopamine neurons in the substantia nigra pars compacta,

but not in the adjacent ventral tegmental area,

and was accompanied by reduced dopamine levels culminating in motor deficits.

This recapitulation of a neurodegenerative cascade thus establishes a mechanistic link between transmission of pathologic α-Syn and the cardinal features of Parkinson’s disease.


J Res Med Sci. 2016 May 9;21:29. eCollection 2016.
Alpha-synuclein structure, functions, and interactions. Emamzadeh FN1.

At present, when a clinical diagnosis of Parkinson's disease (PD) is made, serious damage has already been done to nerve cells of the substantia nigra pars compacta.

The diagnosis of PD in its earlier stages, before this irreversible damage, would be of enormous benefit for future treatment strategies designed to slow or halt the progression of this disease that possibly prevents accumulation of toxic aggregates.

As a molecular biomarker for the detection of Parkinsons disease in its earlier stages, alpha-synuclein (α-syn), which is a key component of Lewy bodies, in which it is found in an aggregated and fibrillar form, has attracted considerable attention.

Here, α-syn is reviewed in details.


J Int Neuropsychol Soc. 2016 Nov;22(10):956-967.
Biomarkers in Prodromal Parkinson Disease: a Qualitative Review. Cooper CA1, Chahine LM1.

Artikel om hypotesen om at Parkinson måske starter i tarmen

thinking about Parkinson’s disease could be wrong.

The condition may arise from damage to the gut

If correct, it opens the door to new ways of treating the disease before symptoms occur.

Many different mechanisms could potentially stop the spread if it start with damage in the gut

Parkinson’s disease involves the death of neurons deep within the brain,

causing tremors, stiffness and difficulty moving.

Some drugs can ease the symptoms, but become less effective as the disease progresses.

One of the hallmarks of the condition is deposits of insoluble fibres of a substance called synuclein.

synuclein is normally found as small soluble molecules in healthy nerve cells,

in people with Parkinson’s synuclein molecules warp into a different shape, making them clump together as fibres.

this transition may start outside the brain

about a decade ago pathologists reported seeing the distinctive synuclein fibres in nerves of the gut during autopsies – both in people with Parkinson’s and in those without symptoms but who had the fibres in their brain.

They suggested the trigger was some unknown microbe or toxin.

people with Parkinson’s often report digestive problems – mainly constipation – starting up to 10 years before they notice tremors.

another early symptom of Parkinson’s is loss of smell.

the nose and gut are two organs where nerve cells are exposed to the outside world – and to potentially problematic toxins and microbes.

synuclein fibres have been shown travelling from the gut to deep within the brain.

Collin Challis at the California Institute of Technology and his colleagues injected synuclein fibres into the stomach and intestine of mice.

Three weeks later the fibres could be seen at the base of the brain, and by two months they had travelled to parts of the brain that control movement.

The mice also became less agile – similar to people with Parkinson’s disease.

The work was reported at the Society for Neuroscience meeting in San Diego august 2016

a growing body of work shows that the gut plays a role in Parkinson’s

people who have had the main nerve to their stomach cut – an old treatment for stomach ulcers – have a lower risk of the
Parkinson condition.

No single bacterium or virus has been pinpointed as the cause.

early evidence suggests that people with Parkinson’s have different gut bacteria to healthy people.

doctors are experimenting with treating patients with antibiotics or faecal transplants.

It could be that having the wrong bacteria in your gut triggers inflammation

inflammation makes synuclein more likely to aggregate

farmers exposed to certain pesticides, are more likely to get Parkinson’s. – and these chemicals can also damage nerves in the gut.

people who get their drinking water from wells – which might be contaminated with pesticides – are more likely to get Parkinson’s. – and these chemicals can also damage nerves in the gut.

drugs that mop up synuclein fibres or block their formation

If these are given to people before the fibres reach the brain they should have a better chance of success.

It might also be possible one day to screen for fibres in the nerves of the gut during colonoscopies for early-stage cancers


Synucleins are a family of soluble proteins common to vertebrates,

primarily expressed in neural tissue

and in certain tumors.[1]

The synuclein family includes three known proteins: alpha-synuclein, beta-synuclein, and gamma-synuclein.

Interest in the synuclein family began when alpha-synuclein was found to be mutated in several families with autosomal dominant Parkinson's disease.[2]

All synucleins have in common a highly conserved alpha-helical lipid-binding motif with similarity to the class-A2 lipid-binding domains of the exchangeable apolipoproteins.

Synuclein family members are not found outside vertebrates, although they have some conserved structural similarity with plant 'late-embryo-abundant' proteins.[1]

Normal cellular functions have not been determined for any of the synuclein proteins.

Some data suggest a role in the regulation of membrane stability and/or turnover.

Mutations in alpha-synuclein are associated with early-onset familial Parkinson's disease

and the protein aggregates abnormally in Parkinson's disease, Alzheimer's disease, Lewy body disease, and other neurodegenerative diseases.[3][4]

The gamma-synuclein protein's expression in breast tumors is a marker for tumor progression.[5][6]

Human proteins containing this domain


  1. George JM (2002). "The synucleins". Genome Biol. 3 (1): REVIEWS3002. doi:10.1186/gb-2001-3-1-reviews3002.PMC 150459Freely accessibleFreely accessible. PMID 11806835.
  2. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, et al. (1997). "Mutation in the alpha-synuclein gene identified in families with Parkinson's disease.". Science. 276 (5321): 2045–7. doi:10.1126/science.276.5321.2045.PMID 9197268.
  3. Mezey E, Dehejia A, Harta G, Papp MI, Polymeropoulos MH, Brownstein MJ (1998). "Alpha synuclein in neurodegenerative disorders: murderer or accomplice?". Nat Med. 4 (7): 755–7. doi:10.1038/nm0798-755. PMID 9662355.
  4. Goedert M (July 2001). "Alpha-synuclein and neurodegenerative diseases". Nat. Rev. Neurosci. 2 (7): 492–501.doi:10.1038/35081564. PMID 11433374.
  5. Ji H, Liu YE, Jia T, Wang M, Liu J, Xiao G, et al. (1997). "Identification of a breast cancer-specific gene, BCSG1, by direct differential cDNA sequencing.". Cancer Res. 57 (4): 759–64. PMID 9044857.
  6. Bruening W, Giasson BI, Klein-Szanto AJ, Lee VM, Trojanowski JQ, Godwin AK (May 2000). "Synucleins are expressed in the majority of breast and ovarian carcinomas and in preneoplastic lesions of the ovary". Cancer. 88 (9): 2154–63.doi:10.1002/(SICI)1097-0142(20000501)88:9<2154::AID-CNCR23>3.0.CO;2-9. PMID 10813729.


Synucleins are small, soluble proteins expressed primarily in neural tissue and in certain tumors.

The family includes three known proteins: α-synuclein, β-synuclein, and γ-synuclein.

All synucleins have in common a highly conserved α-helical lipid-binding motif with similarity to the class-A2 lipid-binding domains of the exchangeable apolipoproteins.

Synuclein family members are not found outside vertebrates, although they have some conserved structural similarity with plant 'late-embryo-abundant' proteins.

The α- and β-synuclein proteins are found primarily in brain tissue, where they are seen mainly in presynaptic terminals.

The γ-synuclein protein is found primarily in the peripheral nervous system and retina, but its expression in breast tumors is a marker for tumor progression.

Normal cellular functions have not been determined for any of the synuclein proteins, although some data suggest a role in the regulation of membrane stability and/or turnover.

Mutations in α-synuclein are associated with rare familial cases of early-onset Parkinson's disease, and the protein accumulates abnormally in Parkinson's disease, Alzheimer's disease, and several other neurodegenerative illnesses.

The current challenge is to understand the normal cellular function of these proteins and how they might contribute to the development of human disease.

Gene organization and evolutionary history

The synuclein family consists of three distinct genes, α-synuclein, β-synuclein, and γ-synuclein, which have so far been described only in vertebrates.

Table 1 catalogs the unique members of the synuclein family that are currently listed in GenBank [1];

these 16 sequences encode the orthologs of each of the three synucleins in the species in which they have been described.

The sequences are shown aligned in Figure 1a and their estimated relationships are indicated by the dendrogram in Figure 1b.

The α-synuclein gene has been mapped to human chromosome 4q21.3-q22 [2],

β-synuclein to human chromosome 5q35 [3], and

γ-synuclein to human chromosome 10q23.2-q23.3 [4].

The α-synuclein gene is organized as 7 exons, 5 of which are protein-coding,

while the β-synuclein gene has 6 exons (5 protein-coding)

and the γ-synuclein gene has 5 exons (all protein-coding) (reviewed in [5]).
Figure 1Alignment and relationships of the 16 known synuclein sequences.

There are about 80 synuclein sequences in GenBank [1], which can be further sorted into 16 unique groups, each representing a single protein-coding sequence orthologous to one of the three synucleins (summarized in Table 1).

(a) The resulting 16 synuclein sequences were aligned with the Multalin program [37].

Shading indicates identity with rat α-synuclein;

blue bars represent the 11-residue repeats.

(b) A dendrogram of synuclein relationships, generated with ClustalW [38] and displayed using TreeView [39].

Table 1
Summary of known synuclein family members
Gene type
Other names
OMIM accession number*
GenBank accession number†
SYN1, SYN2, SYN3 (splice variants)

SYN2 (splice variant)








BCSG1, persyn
Sensory neuron synuclein




Electric ray

*See OMIM [36]; †see GenBank [1].

Characteristic structural features

All synuclein protein sequences consist of a highly conserved amino-terminal domain that includes a variable number of 11-residue repeats and a less-conserved carboxy-terminal domain that includes a preponderance of acidic residues.

The only significant divergences within the repeat domain are the deletion of 11 amino acids (residues 53-63) in all β-synucleins and the addition of a repeat after residue 32 in the γ-synuclein of the electric ray Torpedo californica (Figure 1a).

The 11-mer repeats make up a conserved apolipoprotein-like class-A2 helix (Figure 2a,b), which mediates binding to phospholipid vesicles; lipid binding is accompanied by a large shift in protein secondary structure, from around 3% to over 70% α-helix [6].
Figure 2 Comparison of the amphipathic α-helical domains of α-synuclein and related proteins.

Sequences of interest were imported into Swiss-PdbViewer [40], assigned an ideal α-helical structure, and exported as .pdb files.

Models were then formatted and exported with RASMol [41],

animations (available with the complete version of this article, online) were compiled with QuickTime Pro.

(a) Human α-synuclein residues 1-50, modeled as an α-helix.

The initial frame shown here shows just the hydrophilic face of the helix, with acidic residues confined to the center (red) and basic residues at each interface (yellow); the opposite hydrophobic face (shown in the animation online) contains only uncharged residues (white).

(b) Human apolipoprotein AI residues 190-231;

(c) Arabidopsis thaliana LEA76 residues 1-50;

(d) C. elegans LEA residues 351-400; all are modeled as in (a).

Although no confirmed synuclein orthologs have been identified in non-vertebrates, a low-scoring BLAST 'hit' for similarity is obtained for LEA76, a plant protein belonging to the late embryo-abundant (LEA) group III protein family.

Upon further examination, the sequence similarity is attributable to the presence of an 11-residue repeat encoding a similar class-A2 lipid-binding motif (Figure 2c).

Like synucleins, LEA group III proteins are relatively unordered in solution; upon fast drying, however, they shift to a largely α-helical conformation [7], and are hypothesized to associate with and stabilize cellular membranes against desiccation stress.

A Caenorhabditis elegans LEA homolog has been reported [8] that also shares this structural motif (Figure 2d).

Thus, despite the low degree of primary sequence similarity, further scrutiny of the LEA proteins' potential functional relationships to the synucleins is warranted.

Localization and function

The first synuclein was identified in 1988 by Maroteaux et al. [9],
who screened an expression library with an antiserum raised against purified cholinergic vesicles from the electric organ of the Pacific electric ray Torpedo californica.

This initial cDNA clone (encoding electric-ray γ-synuclein;

Table 1) was used to isolate a rat clone encoding a 140-amino-acid protein (rat α-synuclein, Table 1).

The product of the β-synuclein gene was first isolated as a bovine brain-specific phosphoprotein (phosphoneuroprotein 14 kDa or PNP14),

and its sequence was first described in 1993 [10].

The α- and β-synuclein proteins are predominately expressed in brain,

particularly in the neocortex, hippocampus, striatum, thalamus, and cerebellum;

protein immunoreactivity is enriched at presynaptic terminals [11,12].

Although their normal physiological functions are unknown,

several lines of evidence suggest a role in membrane-associated processes at the presynaptic terminal:

α-synuclein is specifically upregulated in a discrete population of presynaptic terminals of the songbird brain during a period of song-acquisition-related synaptic rearrangement [13];

α- and β-synuclein proteins were biochemically purified from bovine brain as constitutive inhibitors of phospholipase D2 [14], an enzyme that catalyzes the hydrolysis of phosphatidylcholine to phosphatidic acid and appears to play a role in cytoskeletal reorganization and/or endocytosis at the plasma membrane [15];

α-synuclein knockout mice have enhanced dopamine release at nigrostriatal terminals in response to paired electrical stimuli, suggesting that α-synuclein is an activity-dependent negative regulator of dopamine neurotransmission [16];

and, finally, depletion of α-synuclein from cultured primary hippocampal neurons by treatment with antisense oligonucleotides results in a decrease in the distal pool of presynaptic vesicles, as visualized by electron microscopy [17].

Mammalian γ-synuclein was first identified as breast cancer-specific gene 1 (BCSG1) in a high-throughput direct differential-cDNA-sequencing screen for markers of breast cancer [18].

The protein is expressed in the peripheral nervous system (in primary sensory neurons, sympathetic neurons, and motor neurons) [18]

and is also detected in brain [19], ovarian tumors [20], and in the olfactory epithelium [21].

A sequence dubbed synoretin was independently isolated from ocular tissues in a screen for novel proteins regulating phototransduction and is now thought to represent the bovine ortholog of γ-synuclein [22].

The normal cellular function of γ-synuclein is likewise unknown, but exogenous expression of the protein increases the invasive and metastatic potential of breast tumors [23].

Synucleins in neurodegenerative disease

In 1993, Ueda et al. reported [24] that a short peptide (non-amyloid component, NAC) derived from purified amyloid plaques from the brains of people with Alzheimer's disease was derived from a larger precursor protein, non-amyloid component precursor (NACP), which is now known to be identical to human α-synuclein.

Then, in 1997, Polymeropoulos and colleagues reported [25] that a missense mutation (A53T) in α-synuclein was genetically linked to early-onset, familial Parkinson's disease.

Description of a second linked mutation (A30P) followed in 1998 [26].

Antibodies to α-synuclein protein were used to show that the protein accumulates in the ubiquitinated protein inclusions and dystrophic neurites (Lewy bodies and Lewy neurites) that are the hallmark pathological features of the disease; this localization was observed even in cases of sporadic Parkinson's disease, which are not associated with α-synuclein mutations [27].

Indeed, α-synuclein is the primary fibrillar component of Lewy bodies,

and α-synuclein lesions are also observed in cases of dementia with Lewy bodies and multiple system atrophy,

and in some cases of Alzheimer's disease,

the parkinsonism-dementia complex of Guam,

and Hallervorden-Spatz disease (reviewed in [28]).

Although the accumulation of fibrillar α-synuclein in neurodegenerative disease can be interpreted as evidence that the fibrils are themselves toxic, but an equally plausible view is that the fibrils are inert or even protective.

Conway et al. [29] recently observed that the neurotransmitter dopamine forms adducts with α-synuclein that stabilize a protofibrillar form of the protein (at the expense of fibril formation);

the authors proposed that the accumulation of toxic α-synuclein protofibrils could account for the selective loss of dopamine-containing neurons in Parkinson's disease.

The detection of α-synuclein in ubiquitinated inclusions raises the issue of whether α-synuclein is normally targeted for turnover by the ubiquitin-proteasome machinery.

Although the evidence for α-synuclein turnover by the proteasome is equivocal [30,31,32], proteasomal inhibitors do not appear to cause accumulation of polyubiquitinated α-synuclein.

The α-synuclein binding partner synphilin-1 was, however, recently shown to be ubiquitinated and targeted for proteasomal turnover by parkin, a ubiquitin ligase, mutation of which is itself a risk factor for familial Parkinson's disease.

This may provide a common pathological mechanism linking familial mutations in α-synuclein and parkin via their common interactions with synphilin-1 [33].

The β- and γ-synuclein proteins are not found in Lewy bodies,

but β- and γ-synuclein proteins are both associated with hippocampal axon pathology in Parkinson's disease and dementia with Lewy bodies [34].

A change in the expression of γ-synuclein has also been specifically observed in the retina of patients with Alzheimer's disease [22].

The association of synucleins with human disease has focused a great deal of interest on this protein family.

The question of what the synucleins do still remains, however.

Most of the experimental evidence available with regard to function is gleaned from experiments with α-synuclein, but the conservation of an extended, class-A2 amphipathic α helix comprising more than half of each of the protein sequences indicates a common biochemical mechanism among all synucleins, probably involving lipid binding.

Perrin et al. [35] report irreversible multimerization of α-, β-, and γ-synuclein upon exposure to polyunsaturated phospholipid species, cellular membrane components that are the most susceptible to oxidative damage.

This specific interaction might serve to protect these vulnerable lipids from damage

or to scavenge damaged lipids and target them for turnover.

Paxinou et al. [32] also noted recently that α-synuclein is degraded, at least in part, by the lysosome, suggesting a role for α-synuclein in the autophagocytic clearance of damaged cellular organelles.

Thus, it is tempting to speculate that the synucleins help to maintain cellular membrane integrity.

But much work remains to be done to elucidate the normal cellular functions of these unusually conserved proteins

and to determine how they contribute to diverse disease processes spanning neurodegenerative disease and cancer.

Additional data files

Additional data files available with the online version of this article include animated versions of Figure2a, Figure 2b, Figure 2c and Figure 2d, which can be viewed with QuickTime Player. Additional data file 1: Animated version of Figure 2a (MOV 907 KB) Additional data file 2: Animated version of Figure 2b (MOV 1 MB) Additional data file 3: Animated version of Figure 2c (MOV 908 KB) Additional data file 4: Animated version of Figure 2d (MOV 772 KB)


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In recent years, two developments have imparted a new direction to research on the aetiology and pathogenesis of Parkinson's disease.

First, the discovery that a missense mutation in the α-synuclein gene is a rare genetic cause of Parkinson's disease.

Second, the identification of the α-synuclein protein as the main component of Lewy bodies and Lewy neurites, the defining neuropathological characteristics of all cases of Parkinson's and several other diseases.

The filamentous inclusions of multiple system atrophy are also made of α-synuclein.

These findings have placed α-synuclein dysfunction at the centre of several common neurodegenerative diseases.


Parkinson’s Vaccine: EU-Team Launches Clinical Trial

Vaccine candidate based on proprietary technology by AFFiRiS AG

Vienna, 9 December 2014. A novel Parkinson’s vaccine will now be tested in a clinical Phase I trial in Austria by an EU-funded consortium.

The vaccine was developed by the Austrian biotech company AFFiRiS AG and targets a protein called alpha-Synuclein.

The protein plays a key role in the onset and progression of Parkinson’s as well as multiple system atrophy (MSA), an orphan disease.

This vaccine has the potential to modify disease progression, rather than only symptomatic improvements available with current treatment strategies.

The start of the Parkinson’s trial follows in the wake of positive results from a similar Parkinson’s vaccine trial recently conducted by AFFiRiS with support from the Michael J. Fox Foundation.

Today the EU-consortium SYMPATH starts recruitment for a Phase I study of a Parkinson’s vaccine candidate called AFFITOPE® PD03A.

This vaccine is one out of a designated pool of promising vaccine candidates based on AFFiRiS‘ proprietary AFFITOME® technology.

These candidates aim at disease modification of Parkinson’s instead of only ameliorating the severe motor symptoms of the disease, such as tremor.

All vaccines in this pool target alpha-Synuclein, a protein that is key to the onset and the progression of both, Parkinson’s and multiple system atrophy (MSA).

Recently, encouraging clinical results of a Parkinson’s trial of one other of the pool’s vaccines, namely PD01A, were presented by the Michael J. Fox Foundation and AFFiRiS.

These confirmed the safety and tolerability of the vaccine, as well as its ability to induce an immune response and even achieve functional stabilization.

Commenting on the latest clinical trial, Prof. Achim Schneeberger, Chief Medical Officer at AFFiRiS and coordinator of SYMPATH, explains: „The results we achieved with the Parkinson’s vaccine PD01A were very encouraging.

Now, PD03A will be tested in a comparable setting and we are eagerly awaiting the results.

„The current trial of PD03A is a multi-centric patient blinded, randomized, placebo-controlled, parallel group Phase I trial.

It will be conducted in Vienna and Innsbruck, Austria. Prof. Werner Poewe, chairman of the Department of Neurology at the Medical University of Innsbruck and principal investigator of the study, explains the objectives of the trial:

„The primary endpoint of the trial aims to demonstrate the safety and tolerability of the vaccine.

It will also assess the vaccine’s immunological and clinical activity in vaccinated patients as its secondary endpoint.“

Dr. Dieter Volc of PROSENEX Ambulatorium BetriebsgmbH, leading the trial in Vienna, adds:

„PD03A is one of the first medications worldwide aiming for clinical efficacy by modulating the metabolic pathway of alpha-Synuclein.

It has the potential to treat the cause of Parkinson’s – not just the symptoms.“

Current scientific understanding is that Parkinson’s – as well as MSA – is caused by deposits of pathological forms of alpha-Synuclein in the nervous system.

The reduction of pathological alpha-Synuclein levels is believed to have a beneficial impact on the progress of the diseases.

PD03A aims to accomplish this by inducing the production of antibodies that target and promote clearance of alpha-Synuclein in order to neutralize its toxic impact.

The start of the clinical trial comes only a year after the SYMPATH-Consortium was launched.

This rapid progress is owed to the high expertise in Parkinson’s and related diseases of all members of the consortium including the Forschungszentrum Jülich in Germany, the INSERM F-CRIN Toulouse, the Departments of Neurology at the University Hospitals of Bordeaux and Toulouse, France, as well as the Medical University of Innsbruck’s Department of Neurology and PROSENEX, Vienna, Austria.

Additionally, the successful track record of the AFFiRiS AFFITOME® platform that forms the basis of PD01A and PD03A significantly accelerated the vaccine development.

Dr. Markus Mandler, head of the Neurodegeneration Department at AFFiRiS explains:

„Both vaccines are based on AFFiRiS‘ AFFITOME®technology.

This technology delivers not only a single vaccine for the treatment of a certain disease but a whole pool of product candidates with excellent safety profiles and strong specificity to their targets.“

AFFITOME® is registered trademarks of AFFiRiS. Identifier: NCT02267434


SYMPATH („Reach α-synuclein-dependent neurodegeneration: clinical development of therapeutic AFFITOPE vaccines for Parkinson’s disease and multiple system atrophy“) is a collaborative project of the Seventh Framework Programme of the European Union, holding Grant Agreement No. HEALTH-F4-2013-60299.

SYMPATH aims to advance the clinical development of therapeutic vaccines targeting alpha-Synuclein-driven neurodegenerative diseases including Parkinson’s disease (PD) and multiple system atrophy (MSA) where no causal therapy currently exists.

The project will run for 48 months. It has received 5.99 million Euros in funding from the European Union

. AFFiRiS AG located in Vienna, Austria serves as the coordinator for the projects ambitious research program and is supported by Biolution in project management tasks.

Project partners include 5 universities and 3 SMEs:

AFFiRiS AG (Austria) – Prof. Dr. Achim Schneeberger

Biolution GmbH (Austria) – Dr. Iris Grünert

University Hospital Bordeaux (France) – Prof. Wassilios Meissner, MD

INSERM F-CRIN Toulouse (France) – Claire Levy Marchal, MD, MSc

Prosenex Ambulatoriumsbetriebs-GmbH (Austria) – Dieter VOLC, MD

Medical University Innsbruck, Department of Neurology (Austria) – Prof. Werner Poewe, MD & Prof. Klaus Seppi, MD Forschungszentrum Jülich GmbH (Germany) – Prof. Dr. Dieter Willbold

University Hospital Toulouse (France) – Prof. Olivier Rascol, MD

About AFFiRiS AG (By: December 2014)

Based on its proprietary IP positions AFFiRiS develops tailor-made drugs mainly as Peptide-based vaccines.

Target diseases include Alzheimer, Parkinson, Diabetes and other indications with attractive markets and unmet medical need.

Alzheimer is the lead indication.

Current investors are: MIG-Fonds and Athos Service GmbH, both Munich, Germany.

AFFiRiS is located at the campus of the Vienna Biocenter, Vienna Austria and employs 80 highly qualified employees.

About Parkinson’s disease

Parkinson’s disease is the second most common neurodegenerative disorder among the elderly with approximately 1.2 Mio European patients alone

. Currently there is no cure for the disease and existing therapeutic measures are only able to treat its symptoms.

Its classical motor symptoms result from the death of dopamine-generating cells in the substantia nigra, a specific region of the midbrain.

The disease typically starts with non-motor symptoms, progresses slowly but steadily to a debilitating state.

About Multiple System Atrophy

Multiple system atrophy is a rare, orphan status neurodegenerative disorder.

Multiple system atrophy progresses rapidly leading to death of the affected individual within, on average, 6-9 years.

There is currently no cure for the disease.

MSA is associated with the degeneration of nerve cells in specific areas of the brain.

This causes problems with movement, balance, and autonomic functions of the body.

Unlike Parkinson’s disease, where symptomatic treatments are well established, there are no drugs approved for the treatment of MSA.

Contact AFFiRiS AG:

Mag. Julia Bock

Karl-Farkas-Gasse 22

1030 Vienna, Austria

T +43 / (0)1 / 798 15 75 – 303 E


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T +43 / (0)1 / 505 70 44



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