Biosynthesis of AMPA receptors AMPA受体运输.pptVIP

Caspase-6, but not caspase-3, -7 or –8, is activated during serum deprivation-induced human neuronal cell death (LeBlanc et al., 1999). Caspase-6 can cleave APP directly, which may be a pathway to increase A? production (LeBlanc et al., 1999; Pellegrini et al., 1999). Active caspase-6 p10 fragments may increase in AD brains (LeBlanc et al., 1999). Caspase-6 inhibitor can block apoptotic promoting effects of APP-BP1, an APP binding protein (Chen et al., 2000). Caspase-6 may be involved in human neuronal cell death Caspase-6 specific inhibitor can block apoptosis in human neurons (LeBlanc et al., 1999). Implication and Inhibition of Caspase-6 in Human Neuronal Cell Death Yan Zhang Department of Neurology and Neurosurgery McGill University Summary and Conclusions Implication of caspase-6 in human neuronal cell death First direct evidence showing caspase-6 (but not caspase-3) is the key player in human neuronal cell death and may be involved in AD development. Inhibition of caspase-6 in human neuronal cell death First identification of caspase inhibitory factor (CIF), the only natural inhibitor to active caspase-6, induced by 17-?-estradiol at physiological concentrations. Supporting evidence that both estrogen and androgens can be potential candidates for early anti-amyloid therapy for AD. Human Talking mouse = Structural integrity = Functional integrity Acknowledgements Dr. Andréa C. LeBlanc Alzheimer Society Canada for “Doctoral Training Award” Dr. Nathalie Champagne Dr. Lina Musallam Dr. Xavier Roucou Dr. Omar Tounekti Dr. Malcolm Gains Jennifer Hammond Megan Blacker Tracy Petzke Qi Guo Huishan Guo Nicole Quenneville Beverly Akerman Guy Klaiman Younes Bounhar Dr. Stefano Stifani Dr. Bernard Turcotte Dr. Heather Durham Dr. Judes Poirier Dr. Antonis Koromilas Dr. Mark Trifiro Dr. Lenore Beitel Dr. Sylvie Mader Dr. Cynthia Goodyer Estrogen (17-?-estradiol) Cellular ER Signal transduction pathway CIF? Intracellular A?1-42 p53 phosphorylation Upregulate