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简历 王兴龙 1998-2002 年 南京农业大学, 微生物专业 (学士) 2002-2005 年 上海复旦大学 基因工程 (硕士) 2005-2008 年 美国凯斯西储大学 病理学(博士) 2009-2011 年美国凯斯西储大学 病理学(博士后) 2011 年 美国凯斯西储大学 病理学(助教授) 研究方向: 神经退行性的病理机制研究 i Nat Med. 2016 Aug;22(8):869-78. doi: 10.1038/nm.4130. Epub 2016 Jun 27. The inhibition of TDP-43 mitochondrial localization blocks its neuronal toxicity. Wang W 1, Wang L1, Lu J2, Siedlak SL1, Fujioka H3, Liang J4, Jiang S1, Ma X1, Jiang Z1, da Rocha EL5, Sheng M1, Choi H1, Lerou PH6, Li H5, Wang X1. Author information Abstract Genetic mutations in TAR DNA-binding protein 43 (TARDBP, also known as TDP-43) cause amyotrophic lateral sclerosis (ALS), and an increase in the presence of TDP-43 (encoded by TARDBP) in the cytoplasm is a prominent histopathological feature of degenerating neurons in variousneurodegenerative diseases. However, the molecular mechanisms by which TDP-43 contributes to ALS pathophysiology remain elusive. Here we have found that TDP-43 accumulates in the mitochondria of neurons in subjects with ALS or frontotemporal dementia (FTD). Disease-associated mutations increase TDP-43 mitochondrial localization. In mitochondria, wild-type (WT) and mutant TDP-43 preferentially bind mitochondria-transcribed messenger RNAs (mRNAs) encoding respiratory complex I subunits ND3 and ND6, impair their expression and specifically cause complex I disassembly. The suppression of TDP-43 mitochondrial localization abolishes WT and mutant TDP-43-induced mitochondrial dysfunction and neuronal loss, and improves phenotypes of transgenic mutant TDP-43 mice. Thus, our studies link TDP-43 toxicity directly to mitochondrial bioenergetics and propose the targeting of TDP-43 mitochondrial localization as a promising therapeutic approach for neurodegeneration. Pathological mechanisms underlying TDP-43 in neurodegenerative diseases (Nat Med. 2016 Aug;22(8):869-78) Xinglong Wang, Ph.D., Assistant Professor Department of Pathology, Case Western Reserve University 凯斯西储大学 Wolstein Research Building, Rm5122 2103 Cornell Rd, Cleveland, OH 44106 Tel: 216-368-2957; Fax: 216-368-8964; Email: [email protected] 2