Research Laboratories, Toyama Chemical Co., Ltd., Toyama, Japan.
Biochem Biophys Res Commun. 2011 Apr 22;407(4):730-4. doi: 10.1016/j.bbrc.2011.03.091. Epub 2011 Mar 31.
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.
tau 病理学与神经退行性 tau 病的机制有关，包括阿尔茨海默病 (AD) 和与 17 号染色体相关的遗传性额颞叶痴呆和帕金森病 (FTDP-17)。据报道，表达人 tau 的 FTDP-17 突变 P301L 的转基因小鼠 (P301L 小鼠) 表现出广泛的 tau 病理学，并随着年龄的增长表现出行为缺陷。在这项研究中，我们研究了神经保护剂 T-817MA 对 P301L 小鼠神经元退行性相关的运动和认知障碍的影响。T-817MA 可预防 P301L 小鼠运动缺陷的进展和脊髓运动神经元的丢失。此外，T-817MA 显著减轻了 P301L 小鼠空间记忆障碍和海马齿状回突触末梢密度的降低。这些结果表明，T-817MA 通过抑制 P301L 小鼠 tau 病理学引起的神经元退行性改变，改善了运动和认知障碍。因此，预计 T-817MA 具有治疗 AD 等与 tau 相关的神经退行性疾病的潜力。
