cid:image001.jpg@01D158FE.B69B8D00

/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

This email and any attachments may contain confidential, personal and/or privileged information intended for a specific individual and purpose. If you are not the intended recipient, you are hereby notified that any disclosure, copying, retaining, distribution, access, use or modification of the contents of this e-mailed information is strictly prohibited. If you receive this communication in error, please notify the sender immediately and delete or destroy the email message and any attachments or copies. ******************************************

http://www.manitobaneuroscience.ca/ cid:image003.jpg@01D159B3.9F0B9710

https://www.facebook.com/manitobaneuroscience/?fref=ts cid:image007.png@01D29326.7E26D480 https://www.instagram.com/manitobaneuroscience/ cid:image009.jpg@01D29326. 7E26D480 https://twitter.com/manitobaneuro cid:image010.png@01D29326.7E26D480