A recent publication in Science, (Nov. 18, 2016) has shared results of research in mice, that is opening hopeful pathways towards an eventual cure for Alzheimer’s Disease. Scientists at the University of New South Wales, Australia, have made important strides in Alzheimer’s research that could unlock the mystery of the debilitating disease. The study suggests the condition can be prevented by stopping the malfunction of a single protein in the brain.
This study is different from much of the research currently underway on Alzheimer’s which centers around beta-amyloid levels in the brain, suspected of causing plaques associated with the disease. The study by Scientists in New South Wales, centres on research in mice, whereby manipulation of the tau protein via the enzyme p38γ kinase was undertaken.
The protein, called tau protein, normally functions as a stabilizer for the microtubules that act as rails for transporting materials around the cell. 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.
Professor Lars Ittner at the University of New South Wales, Australia, and his colleagues have pinpointed this crucial enzyme that controls how tau proteins behave in the brain. Professor Lars Ittner’s research focuses on understanding disease mechanisms in neurodegeneration and developing therapeutic approaches to overcome dementia.
For more information, visit the Dementia Research Unit homepage (https://medicalsciences.med.unsw.edu.au/research/groups/dementia-research-unit).
As New Scientist reported (November, 2016), studies have suggested problems with the tau protein is somehow linked to Alzheimer’s. The protein can clump together in twisted tangles and could be releasing Alzheimer’s-inducing toxic chemicals. Alzheimer’s disease may be prevented by stopping a crucial brain protein from turning rogue, as the 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. (https://www.newscientist.com/article/2113189-stopping-brain-protein-from-going-rogue-may-prevent-alzheimers/)
The Study Abstract states:
‘Site-specific phosphorylation of tau inhibits amyloid-β toxicity in Alzheimer’s mice.
Alzheimer’s disease presents with amyloid-β (Aβ) plaques and tau tangles. The prevailing idea in the field is that Aβ induces phosphorylation of tau, which in turn mediates neuronal dysfunction. Working in Alzheimer’s disease mouse models, Ittner et al. found evidence for a protective role of tau in early Alzheimer’s disease. This protection involves specific tau phosphorylation at threonine 205 at the postsynapse. A protective role of phosphorylated tau in disease challenges the dogma that tau phosphorylation only mediates toxic processes.’ (http://science.sciencemag.org/content/354/6314/904)
The enzyme, called p38γ kinase, seems to block symptoms of Alzheimer’s by interfering with the action of another problem protein, called beta-amyloid. Like tau, clumps of this 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. But Ittner’s team found that 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 mice do not develop Alzheimer’s-like symptoms.
In people, the levels of this enzyme decline significantly as Alzheimer’s progresses, hinting that boosting this enzyme could help prevent or treat the disease.
Itner stated: “One reason why Alzheimer’s treatments that have shown promise in mice have frequently failed in clinical trials, is because earlier mouse models were designed to only mimic beta-amyloid plaque formation in humans.”
Ittner’s study instead used mice that were engineered to recreate the beta-amyloid-tau relationship in humans, so the results should be more applicable to people.
For more information, about the work of Professor Lars Ittner, visit Dementia Research Unit: (https://medicalsciences.med.unsw.edu.au/research/groups/dementia-research-unit).