生命科学前沿容讲座课件.pptVIP

Prion 疾病(prion disease)  疯牛病(Bovine spongiform encephalopathy, BSE) 克雅病(Creutzfeldt-Jacob disease, CJD) 物种间传播 - ransmission from one species to another - the species barrier 食物是否安全 - The important question now is of course is food now safe from contamination with BSE and hence from a risk of contracting CJD? - No evidence to show safety or not (low or high risk instead). 政治和经济因素 - Political and economic issues – UK, EU, USA, Japan Global view of the amino acid sequence of PrP What does normal PrP do? 1997: Stanley Prusiner proposed a link between kuru, CJD, scrapie and BSE. -Proposed that “prion” was responsible for spongiform manifestations in BSE-infected patients DEFINITION: PRION = Proteinaceous Infectious Particles Prion protein exists in two forms: PrPc vs. PrPsc Prion folding model as link between chemistry and biologyWhat do folding rates and equilibrium constants mean? One protein: Two structures Not all pretty pictures can be trusted! the prion hypothesis Effects of TSEs on the brain What makes prion a prion? Why don’t other proteins adopt two drastically different stably folded conformations? A helix is a helix…but why are helices in prion protein likely to undergo a big structural change? “Big picture” questions as a platform for development of testable hypotheses Why would nature evolve prions? How would you tell a prion if you saw one? Yeast prions do not cause a disease. Are there other non-harmful prion-like proteins? Can prions be beneficial? 现已确定，一大类人和动物慢性、亚急性中枢神经系统的退行性疾病均与Prion有关(人类:散发性Prion病CiD；遗传性Prion病家族性CJD；GSS；致死性家族性失眠症；传染性Prion病kuru病；医源性CJD。动物：自然性羊瘙痒症；自然性羊瘙痒症；BSE；猫海绵状膳病；传染性水韶脑病；慢性废墟病；实验性羊瘙痒症；自然性羊瘙痒症。)，其临床特点为：(1)遗传的，或传染的，或散发的； (2)潜伏期长，可达数年或十数年至数十年；(3)临床上主要表现为中枢神经系统的异常；(4)病情进展迅速，可很快导致死亡。 CJD： 罕见，但CJD是最常见的人类TSE。 CJD可以是遗传的、传染的或散发的，近15％的病例为家族性，不到1％的为传染性获得，85％为散发性病例，病因不明。CJD的年发病率约为百万分之一，男、女性之比为1：1．2，常累及50岁～75岁年龄段人群，平均发病年龄为65岁左右，潜伏期15个月～10年，最长可在40年以上。其典型临床表现为进展迅速的痴呆、肌阵挛、皮质盲、小脑共济失调，及椎体束和椎体外系征。CJD的病程可以分为三个阶段：前驱期、进展期、终末期