Mechanism that Triggers Alzheimer’s Pathology is Identified!

Tau accumulation in the Alzheimer's brain can be triggered by a specific chemical feature of the protein as per a study at the Tokyo Metropolitan University. The disulfide bonds on certain amino acids act to stabilize tau and promote its accumulation. This is even more worsened with increased oxidative stress. Alzheimer's disease (AD) is a neurodegenerative disease that leads to gradual memory loss and behavioral changes. It is characterized by the formation of tau tangles and beta-amyloid plaques in the brain tissues, years before the actual symptoms occur.

The healthy function of biological cells is maintained by tau protein. However pathological clumping of these tau protein aggregates blocks the firing of neurons, leading to a wide range of other neurodegenerative diseases known as tauopathies.

Molecular Mechanism for Tau Toxicity

The study team found that alterations to amino acid residues in the protein known as cysteines in two different locations (C291 and C322) had a drastic effect on the amount and toxicity of tau.

Moreover, the disulfide bonds formed by these cysteine groups and exposure to an environment with elevated levels of reactive oxygen species (as thiol groups on the cysteines were oxidized to form disulfide links) were responsible for making the tau proteins even more toxic to normal cell function.

The effect was overcome by the co-expression of antioxidants that helped natural processes clear away tau proteins and dramatically reduce the tau levels.

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Thus identifying these chemical targets that trigger tau accumulation may lead to the formulation of new breakthrough treatments for Alzheimer’s disease and other tauopathies.

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Source-Medindia