北大神经生物学ppt课件6-2神经系统退行性疾病基础.pptVIP

1 1 1 1 1 Our findings indicate that the pathogenic role of the PS-1 mutation is upstream of the amyloid cascade. 1 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 What is Presenilin, APP and Ab ?   崔德华 DH Chui Molecular features of presenilin and APP 崔德华 DH Chui Molecular features of APP and Ab peptides APP : Amyloid precursor protein 崔德华 DH Chui presenilin (Psn） Ab?? APP ???secretase A? Presenilin complex 崔德华 DH Chui Aggregation of ?-amyloid is a multi step process 崔德华 DH Chui Courtesy: Prof. C. Glabe, UC Irvine 崔德华 DH Chui Proposed actions of heat shock protein 70 and heat shock protein 40 chaperones on amyloid assembly NATURE REVIEWS | NEUROSCIENCE VOLUME 6 | JANUARY 2005 | 15 崔德华 DH Chui Direct and indirect effects of molecular chaperones on disease protein toxicity NATURE REVIEWS | NEUROSCIENCE VOLUME 6 | JANUARY 2005 | 15 崔德华 DH Chui Protein misfolding diseases associated with molecular chaperones NATURE REVIEWS | NEUROSCIENCE VOLUME 6 | JANUARY 2005 | 15 崔德华 DH Chui  PresenilinAb cascades in AD  崔德华 DH Chui Transgenic mice with presenilin 1 mutations hPS1/ FVB/ N mice Microinjection method FVB/N mice 2) pAxCAwt-vector 3) h-PDGF promoter 4) hPS1-L286V-cDNA hPS1-H163R-cDNA Chui, DH. et al. Nat Med 5, 560-4. (1999) 崔德华 DH Chui Dark neuron counts are significantly higherr in aged PS1 mutant mice without amyloid plaque formation Chui, DH. et al. Nat Med 5, 560-4. (1999) 崔德华 DH Chui Neurons with intracellular Ab-positive deposits Chui, D.H. et al. Nat Med 5, 560-4. (1999) 崔德华 DH Chui Analysis of apoptosis by double staining with Ab42 (green) and TUNEL (red) PS1 FAD iAb42-negative / TUNEL+ iAb42-positive / TUNEL+ % Mean, SEM 0.05 0.10 *@ 0.00 Chui et al, J Alzheimers Dis. 2001 Apr;3(2):231-239 Chui, DH. et al. J of Alzheimer Disease. 2001; 3: 231 崔德华 DH Chui Impairment of LTP in brain of 3 x TG 崔德华 DH Chui Ab Amyloid aggregations Senile plaques PHF-Tau Neuronal death APP Ab