https://www.newscientist.com/article/2113189-stopping-brain-protein-from-going-rogue-may-prevent-alzheimers/ Alzheimer’s disease may be prevented by stopping a crucial brain protein from turning rogue, a study in mice suggests. Tau protein has long been suspected to play a role in causing the condition. In healthy brains, tau is essential for normal cell functioning. But during Alzheimer’s disease, the protein goes haywire, clumping together and becoming toxic. Eventually, tau forms large, twisted tangles, but it is thought that it is smaller clumps of this protein that damage the brain. Scientists have noted a crucial enzyme that controls how tau proteins behave in the brain. The enzyme, called p38γ kinase, helps keep tau in a healthy, tangle-free state, preventing the onset of memory loss and other symptoms in mice that have been bred to develop a range of Alzheimer’s-like pathologies. The enzyme block symptoms of Alzheimer’s by interfering with the action of another problem protein, called beta-amyloid protein. Clumps of beta-amyloid protein accumulate in the brains of people with Alzheimer’s, making it another suspected cause of the disease. When beta-amyloid forms these sticky plaques, it can also modify the structure of tau proteins, causing them to become toxic and form tangles. p38γ kinase makes a different kind of structural change to tau. If this change is made first, it prevents beta-amyloid from being able to turn tau bad, and then mice do not develop Alzheimer’s-like symptoms. In people, the levels of this enzyme p38γ kinase decline significantly as Alzheimer’s progresses Therefore boosting this enzyme could help prevent or treat the disease. Using an enzyme to stop tau from becoming toxic is novel – most research has focused on targeting beta-amyloid We have treatments that decrease beta-amyloid levels, but they don’t have much efficacy Animal work is increasingly showing that beta-amyloid toxicity is mediated through tau In earlier studies mouse models were designed to only mimic beta-amyloid plaque formation in humans
The new study used mice that were engineered to recreate the beta-amyloid-tau relationship in humans, so the results is more applicable to people Journal reference: Science, DOI: 10.1126/science.aah6205 Read more: Superagers with amazing memories have Alzheimer’s brain plaques
https://www.sciencedaily.com/releases/2016/11/161117151205.htm Australian researchers have shed new light on the nerve cell processes that lead to Alzheimer's disease (AD), This study is overturning previously held ideas of how the disease develops The study is opening the door to new treatment options that could halt or slow its progression.
The study is published in the journal Science. The protein, kinase p38γ, is lost as AD progresses. When the scientists reintroduced the protein into the brains of mice, it had a protective effect against memory deficits associated with the disease. This study has completely changed our understanding of what happens in the brain during the development of Alzheimer's disease," said lead author UNSW Professor Lars Ittner. Two of the hallmarks of Alzheimer's are the presence of protein plaques (made up of amyloid-beta) and tangles (made up of tau protein) in the brain. The accumulation of these plaques and tangles is associated with cell death, brain atrophy and memory loss. A crucial step in the process that leads to tangles has been misunderstood. Scientists believed the plaque-forming protein, amyloid-beta, caused a modification — called phosphorylation — to the tau protein resulting in cell death and Alzheimer's disease. Increased phosphorylation of tau eventually leads to its accumulation as tangles. The new study suggest that the phosphorylation of tau initially has a protective effect on neurons, and that amyloid-beta assaults the protective functionality until it is progressively lost. This is the stage at which toxicity levels cause the destruction of neurons and results in the cognitive deficits associated with Alzheimer's disease. Amyloid-beta induces toxicity in the neurons but the first step in tau phosphorylation is actually to decrease this toxicity. This is a completely new mindset; that the reason tau becomes modified is actually to protect from damage. A protein called kinase p38γ assist the protective phosphorylation of tau p38γ is lost as AD progresses, however a small amount does remain in the brain. By reintroducing p38γ – thereby increasing its activity, it could prevent memory deficits from happening, so it has true therapeutic potential. If we can stimulate that activity, we may be able to delay or even halt the progression of Alzheimer's disease.
Site-specific phosphorylation of tau inhibits amyloid- toxicity in Alzheimers mice. Science, 2016; 354 (6314): 904 DOI: 10.1126/science.aah6205=