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/sent on behalf of Susan Zettler
Date: June 7, 2018 Time: 1:30 PM �C 2:30 PM Location: Samuel N. Cohen Auditorium, St. Boniface Hospital Albrechtsen Research Centre
Deborah Toiber, PhD
Senior Lecturer
Department of Life Sciences
Ben-Gurion University of the Negev
Beer-Sheva, Israel
Topic: NEUROPROTECTIVE FUNCTIONS FOR THE HISTONE DEACETYLASE SIRT6
Neurodegenerative diseases are caused by the loss of neuronal cells. For many years, researchers have been trying to find the causes and possible therapies for the diverse neurodegenerative pathologies. Yet, distinguishing between the causes and the consequences of neurodegeneration is difficult, as all the symptoms and markers get tangled in an array of phenotypes. The most accepted theory of aging is that the accumulation of unrepaired DNA damage is the main cause: As we age, we accumulate DNA lesions, until we reach a threshold of irreparable lesions. The histone deacetylase SIRT6 has been linked to the aging process. SIRT6 knockout mice exhibit an accelerated aging phenotype and die prematurely. SIRT6 promotes DNA repair, but its activity declines with age with a concomitant accumulation of DNA damage. We report that brain-specific SIRT6-deficient mice survive but present behavioral defects with major learning impairments by 4 months of age. Moreover, the brains of these mice show increased signs of DNA damage, cell death, and hyperphosphorylated Tau-a critical mark in several neurodegenerative diseases. Mechanistically, SIRT6 regulates Tau protein stability and phosphorylation through increased activation of the kinase GSK3��/��. Finally, SIRT6 mRNA and protein levels are reduced in patients with Alzheimer's disease. Taken together, our results suggest that SIRT6 is critical to maintain genomic stability in the brain and that its loss leads to toxic Tau stability and phosphorylation. Therefore, SIRT6 and its downstream signaling could be targeted in Alzheimer's disease and age-related neurodegeneration.
For further information, please contact the CCARM
Administration Office
Tel: 235-3455 email: ccarm@sbrc.ca
Kelly Jorundson Coordinator, Membership & Operations Manitoba Neuroscience Network
Email: kjorund@sbrc.ca Tel: 204.235.3939 Fax: 204.237.4092
St. Boniface Hospital Albrechtsen Research Centre Room R4046 - 351 Tach�� Avenue, Winnipeg, MB R2H 2A6 CANADA
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