/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 GSK3α/β. 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 Taché  Avenue,  Winnipeg, MB  R2H 2A6  CANADA

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