T-817MA, a neuroprotective agent, attenuates the motor and cognitive impairments associated with neuronal degeneration in P301L tau transgenic mice |
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Authors: | Fukushima Tetsuo Nakamura Asako Iwakami Noboru Nakada Yasushi Hattori Hiroshi Hoki Satoru Yamaguchi Hidetoshi Nakagawa Masaya Terashima Nobuo Narita Hirokazu |
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Institution: | Research Laboratories, Toyama Chemical Co., Ltd., Toyama, Japan |
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Abstract: | Tau pathology is implicated in mechanisms of neurodegenerative tauopathies, including Alzheimer’s disease (AD) and hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). It has been reported that transgenic mice expressing FTDP-17 mutation P301L of human tau (P301L mice) display extensive tau pathology and exhibit behavioral deficits with aging. In this study, we investigated the effects of T-817MA, a neuroprotective agent, on the motor and cognitive impairments associated with neuronal degeneration in P301L mice. T-817MA prevented the progression of motor deficit and the loss of spinal cord motor neurons in P301L mice. Furthermore, T-817MA significantly attenuated the spatial memory impairment and the reduction in synaptic terminal density in the hippocampal dentate gyrus of P301L mice. These results indicate that T-817MA improved the motor and cognitive impairments as a result of inhibiting neuronal degeneration derived from tau pathology in the P301L mice. Therefore, it is expected that T-817MA has a therapeutic potential for tau-related neurodegenerative diseases such as AD. |
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Keywords: | Abbreviations: AD Alzheimer&rsquo s disease FTDP-17 frontotemporal dementia and parkinsonism linked to chromosome 17 P301L mice transgenic mice expressing FTDP-17 mutation P301L of human tau T-817MA 1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl} azetidin-3-ol maleate Aβ amyloid-β NFT neurofibrillary tangles ROS reactive oxygen species DG dentate gyrus WT wild type |
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