生命科学挑战班系列讲座
题目：Molecular Neurobiology of Alzheimer’s Disease.
报告人：Sangram S. Sisodia, Ph.D.
Thomas Reynolds Sr. Family Professor of Neurosciences
Department of Neurobiology and Neurology
The University of Chicago, Chicago, Il. 60637 USA
时间：2013年12月16日（周一）下午13:00-14:00 PM
地点：新生物楼101报告厅
Alzheimer’s disease is a progressive neurodegenerative disease that is pathologically characterized by the presence of senile plaques, composed of A peptides that are derived from amyloid precursor proteins (APP). Inheritance of mutant genes encoding APP and presenilins (PS) variants cause autosomal dominant, familial Alzheimer`s disease (FAD). PS is the catalytic subunit of the-secretase complex that is essential for intramembranous processing of APP, Notch and several type I membrane proteins and I will present studies aimed at elucidating the structure and activity of the secretase complex that is composed of PS, PEN-2, Aph1 and nicastrin (NCT). In parallel studies, we have examined transgenic mice in which the FAD-linked PS1 E9 transgene can be conditionally deleted in a spatial and temporal manner in order to investigate the impact of mutant PS1 on the proliferation and differentiation of adult hippocampal progenitor cells as a function of environmental enrichment (EE) and exercise. We have shown that excitatory neurons play a critical role in EE-mediated effects EE on hippocampal progenitors (Veeraraghavalu and Sisodia, PNAS, 2013), and I will discuss studies to evaluate the nature of the signaling molecules involved in these processes. Moreover, we have demonstrated that EE and exercise can largely attenuate A deposition in transgenic mice expressing mutant APP and PS1 variants (Lazarov et al, Cell, 2005) and that conditional deletion of the PS1 E9 transgene in excitatory neurons has a significant in attenuating these phenotypes. In summary, I will present an overview of the molecular and cellular mechanisms by which FAD-linked mutant genes encoding mutant APP and PS1 variants cause Alzheimer’s disease.
Supported by NIH AG027854 (SSS), Alzheimer’s Association, AHAF, the Edward H. Levi Fund, Adler Foundation and Cure Alzheimer’s Fund (CAF). SSS is a paid Consultant of Eisai Research Labs Inc.
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