title: T-817MA, a neuroprotective agent, attenuates the motor and cognitive impairments associated with neuronal degeneration in P301L tau transgenic mice.
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.
authors: Research Laboratories, Toyama Chemical Co., Ltd., Toyama, Japan. tetuo_fukushima@toyama-chemical.co.jp
authors: Tetsuo
authors: T
authors: Fukushima
authors: Asako
authors: A
authors: Nakamura
authors: Noboru
authors: N
authors: Iwakami
authors: Yasushi
authors: Y
authors: Nakada
authors: Hiroshi
authors: H
authors: Hattori
authors: Satoru
authors: S
authors: Hoki
authors: Hidetoshi
authors: H
authors: Yamaguchi
authors: Masaya
authors: M
authors: Nakagawa
authors: Nobuo
authors: N
authors: Terashima
authors: Hirokazu
authors: H
authors: Narita
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology; D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008298:Maleates / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D009069:Movement Disorders / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016708:Synaptophysin / Q000378:metabolism; D013876:Thiophenes / Q000627:therapeutic use*; D016875:tau Proteins / Q000235:genetics
chemical_list: C503102:1-(3-(2-(1-benzothiophen-5-yl) ethoxy) propyl)-3-azetidinol maleate; D008298:Maleates; C558298:Mapt protein, mouse; D018696:Neuroprotective Agents; D016708:Synaptophysin; D013876:Thiophenes; D016875:tau Proteins