Reference - Detail
|Author||Miyasaka T, Ding Z, Gengyo-Ando K, Oue M, Yamaguchi H, Mitani S, Ihara Y.|
|Title||Progressive neurodegeneration in C. elegans model of tauopathy.|
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.
|MeSH||Animals Animals, Genetically Modified Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Disease Models, Animal Glycogen Synthase Kinase 3 / genetics Glycogen Synthase Kinase 3 / metabolism Glycogen Synthase Kinase 3 beta HSP70 Heat-Shock Proteins / genetics HSP70 Heat-Shock Proteins / metabolism Immunohistochemistry Mechanoreceptors / metabolism Mechanoreceptors / pathology Mechanoreceptors / ultrastructure Microscopy, Electron, Transmission Microtubules / metabolism Microtubules / pathology Microtubules / ultrastructure Mutation / genetics Nerve Degeneration / metabolism* Nerve Degeneration / pathology Nerve Degeneration / physiopathology Nervous System / metabolism* Nervous System / pathology Nervous System / physiopathology Neurites / metabolism Neurites / pathology Neurites / ultrastructure Neurons / metabolism Neurons / pathology Neurons / ultrastructure Oxidative Stress / genetics Somatosensory Disorders / metabolism Somatosensory Disorders / pathology Somatosensory Disorders / physiopathology Tauopathies / metabolism* Tauopathies / pathology Tauopathies / physiopathology Touch / genetics tau Proteins / genetics tau Proteins / metabolism|