Israeli scientists at Ben-Gurion University of the Negev (BGU) have made significant progress in determining the causes of neurodegenerative diseases in the elderly, including Alzheimer’s and Parkinson’s.
Aging is the main factor in the development of a neurodegenerative disease. The common consensus is that aging is the result of the accumulation of damage to DNA, essentially a result of the body’s failure to implement processes to completely repair its DNA over the years. Sporadic Alzheimer’s disease affects about 50% of people over 90, suggesting that the causes are mainly age related.
A study titled Neuroprotective Functions for the Histone Deacetylase SIRT6 led by Dr. Deborah Toiber of the Department of Life Sciences at BGU using mice showed that levels of the stress responsive protein Sirtuin-6 (SIRT6) are correlated with DNA repair functions. A decrease in SIRT6 protein levels resulted in increased DNA damage and preceded other indications of neurodegenerative diseases, such as the Tau and GSK-3 proteins, which are related to the pathogenesis of Alzheimer’s disease. SIRT6 was nearly completely absent in patients with Alzheimer’s disease.
“Overall, we found that SIRT6 depletion in the brain, which occurs during aging and in Alzheimer’s, results in increased GSK-3 activity, Tau-p, DNA-damage-induced neurodegeneration, and behavioral defects, all of which might be linked to a brain-specific SIRT6-GSK3 axis,” states the study published in the Cell Reports journal.
Essentially, high levels of SIRT6 contribute to DNA repair while low levels permit DNA damage accumulation.
According to Dr. Toiber, “if a decrease in SIRT6 (and lack of DNA repair) is the beginning of the chain that ends in neurodegenerative diseases in seniors, then we should be focusing our research on how to maintain production of SIRT6 and avoid the DNA damage that leads to these diseases.”
Dr. Toiber’s lab is one of just a handful around the world that looks at the effects of SIRT6 in the brain.
By: Ilana Messika