课程名称︰分子神经病理学 课程性质︰选修 课程教师︰廖永丰/陈志成 开课学院：生命科学院 开课系所︰生命科学系 考试日期（年月日）︰2018/06/14 考试时限（分钟）：180 试题 : Please answer the following questions concisely. 廖永丰部分 Please write your answers to questions 1-4 in one sheet of exam paper.(YL and LHY) 1.(i) Please describe how you can prove that Abeta-elicited neurotoxicity results from its oligomeric form, but not its fibrillar form. (4 pts.) (ii) Accumulating evidence has strongly suggested that both Abeta- and Tau-elicited toxicity can contribute to the pathogenesis of Alzheimer's disease (AD). Please describe one experimental conclusion supporting the notion that the crosstalk between Abeta- and Tau-elicited signaling can instigate AD. (6 pts.) 2.(i) The pathogenesis of Parkinson's disease (PD) has been linked to the increased level of alpha-synuclein in neurons. Please propose one therapeutic strategy that targets the alpha-synuclein-mediated neurodegeneration in PD. (6 pts.) (ii) Mitochondrial dysfunction seems to play a central role in PD pathogenesis. Please describe one potential disease-modifying therapy for PD that targets mitochondrial dysfunction and how this potential therapy works. (4 pts.) 3. Hu et al. (J. Exp. Med., 215:927-940, 2018) showed that BACE1 deletion in the adult mouse can reduce Abeta deposition and improve cognitve functions In light of recently reported failure in the randomized trial of Verubecestat (a BACE1 inhibitor) for AD, in which treatments with the BACE1 inhibitor do not reduce cognitive decline in patients with mild-to-moderate AD (N. Engl. J. Med., 378:1691-703, 2018), how would you reconcile the different conclusions between the results from the animal study and human trial? (5 pts.) 4. Please briefly discuss how the genomic lesions selectively impact the nervous system in a cell type-specific manner. (10 pts.) 陈志成部分 Please write your answers to questions 5-7 in the other sheet of exam paper. (CC) 5. Huntington disease is an inheritable neurodegenerative disease. Please describe the genetic component causing the disease (1 pt) and how the gene mutation affects the neurons in terms of loss of function and gain of function (9 pts.). 6. (a) Please describe the hypothesis and establoshed models to assay anxiety-like behaviors in mice. (4 pts.) (b) Please describe the underlying mechanisms that contribute to LPS-induced sickness and depression-like symptoms; and how to distinguish these two symptoms in animal behaviors. (6 pts.) 7. Please describe one of the key experiments that can demonstrate skeletal muscle is involved in sleep regulation. (5 pts.) Exam time: 3h. Format: open-book. --

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