Progressive neurodegeneration in C. elegans model of tauopathy

Neurobiology of Disease

Keiko Gengyo-Ando¹  Zhen Ding²  Tomohiro Miyasaka²  Haruyasu Yamaguchi³  Yasuo Ihara⁴  Miho Oue⁴  Shohei Mitani⁵ 

[1] Department of Physiology, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjyuku-ku, Tokyo 152-8666, Japan;Department of Neuropathology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan;Department of Parasitology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi 371-8511, Japan;Department of Physiology, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjyuku-ku, Tokyo 152-8666, Japan;Gunma University School of Health Sciences, 3-39-15 Showa-machi, Maebashi 371-8514, Japan;

关键词: tau;    C. elegans;    FTDP-17;    Tauopathy;    Touch neuron;    Neurodegeneration;   

DOI  :  

来源: DOAJ

【 摘 要 】

Discovery of various mutations in the tau gene among frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) families suggests gain-of-toxic function of wild-type or mutant tau as the mechanism for extensive neuronal loss. We thus generated transgenic nematode (Caenorhabditis elegans) expressing wild-type or mutant (P301L and R406W) tau in the touch (mechanosensory) neurons. Whereas the worm expressing wild-type tau showed a small decrease in the touch response across the lifespan, the worm expressing mutant tau displayed a large and progressive decrease. When the touch neurons lost their function, neuritic abnormalities were found prominent, and microtubular loss became remarkable in the later stage. A substantial fraction of degenerating neurons developed tau accumulation in the cell body and neuronal processes. This neuronal dysfunction is not related to the apoptotic process because little recovery from touch abnormality was observed in the ced-3 or ced-4-deficient background. Expression of GSK3 brought about slight deterioration in the touch response, while expression of HSP70 led to some improvement.

【 授权许可】

Unknown