北大神经生物学ppt课件6-3神经系统退行性疾病基础.pptVIP

代理报关委托书委托报关协议关于审理城镇房屋租赁合同纠纷案件司法解释有关劳务派遣制度设计及对劳务派遣行业的影响分析糖皮质激素在呼吸系统疾病中的合理应用严重脓毒症导致急性肺损伤病人自发利尿现象的观察分析 Immunoblotting analysis, immunocytochemical staining and double immunostaining in AD brain Oyagi, Asahara, Chui et al. FASEB J. 2005 崔德华 DH Chui Summary (3) Intracellular A?42 directly activated the p53 promoter resulting in p53-dependent apoptosis. Remarkably, accumulation of both A?42 and p53 was found in some degenerating-shape neurons in both mice and AD cases. Thus, the intracellular A?42/p53 pathway may be directly relevant to neuronal loss in AD. Intracellular A?42 may cause p53-dependent neuronal apoptosis through activation of the p53 promoter; thus demonstrating an alternative pathogenesis in AD. Oyagi, Asahara, Chui et al. FASEB J. 2005 崔德华 DH Chui Structure of Human GSK3 崔德华 DH Chui GSK-3a is required for Ab production CHO-APP695 cells were transfected with GFP or GSK-3a, and secreted Ab42 崔德华 DH Chui Lithium blocks Ab accumulation in cultured neurons and in the brains of mice overproducing Ab peptides Embryonic cortical neurons were infected with SFV containing wild-type APP (APP-WT) or APP-Swedish (KM670/671NL), then treated with LiCl for 24 h. 崔德华 DH Chui 崔德华 DH Chui Effects of GSK-3b on AD GSK-3b oAb NFT formation Neuronal loss Synapse loss Memory loss Akt kinesin Tau accumulation GSK-3? Inhibitor tau This suggests that inhibiting GSK-3? is a promising AD therapy p53 Axonal transport degradation 崔德华 DH Chui Therapeutic Approach for Alzheimer Disease 崔德华 DH Chui Therapeutic Approach for Alzheimer Disease 1. AD的一般护理、经济、法律2. 西医药治疗 胆碱酯酶抑制剂疗法 AD的新免疫疗法 抗炎疗法 gama和beta-APP分泌酶抑制剂疗法 GSK-3beta抑制剂疗法 其他3.中医药治疗 崔德华 DH Chui 乙酰胆碱与AD 1）中枢乙酰胆碱含量下降、胆碱乙酰化酶（ChAT）、胆碱酯酶 （AchE）活性降低或乙酰胆碱受体（M-AchR、N-AchR）敏感性降低是 AD的主要病理改变之一。 2）胆碱能神经元主要位于纹状体、伏隔核、嗅结节、海马和皮质2-4层 崔德华 DH Chui Acetylcholine a) Ach synthesis b) Ach degradation Tau 崔德华 DH Chui Memory loss-Dementia Alzheimer disease 崔德华 DH Chui 胆碱抑制剂与AD 胆碱抑制剂； 安