Kuboyama Tomoharu, Hirotsu Keisuke, Arai Tetsuya, Yamasaki Hiroo, Tohda Chihiro
Division of Neuromedical Science, Institute of Natural Medicine, University of Toyama, Toyama, Japan.
R&D Center, Kobayashi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Front Pharmacol. 2017 Nov 14;8:805. doi: 10.3389/fphar.2017.00805. eCollection 2017.
Memory impairments in Alzheimer's disease (AD) occur due to degenerated axons and disrupted neural networks. Since only limited recovery is possible after the destruction of neural networks, preventing axonal degeneration during the early stages of disease progression is necessary to prevent AD. Polygalae Radix (roots of ; PR) is a traditional herbal medicine used for sedation and amnesia. In this study, we aimed to clarify and analyze the preventive effects of PR against memory deficits in a transgenic AD mouse model, 5XFAD. 5XFAD mice demonstrated memory deficits at the age of 5 months. Thus, the water extract of Polygalae Radix (PR extract) was orally administered to 4-month-old 5XFAD mice that did not show signs of memory impairment. After consecutive administrations for 56 days, the PR extract prevented cognitive deficit and axon degeneration associated with the accumulation of amyloid β (Aβ) plaques in the perirhinal cortex of the 5XFAD mice. PR extract did not influence the formation of Aβ plaques in the brain of the 5XFAD mice. In cultured neurons, the PR extract prevented axonal growth cone collapse and axonal atrophy induced by Aβ. Additionally, it prevented Aβ-induced endocytosis at the growth cone of cultured neurons. Our previous study reported that endocytosis inhibition was enough to prevent Aβ-induced growth cone collapse, axonal degeneration, and memory impairments. Therefore, the PR extract possibly prevented axonal degeneration and memory impairment by inhibiting endocytosis. PR is the first preventive drug candidate for AD that inhibits endocytosis in neurons.
阿尔茨海默病（AD）中的记忆障碍是由于轴突退化和神经网络破坏所致。由于神经网络破坏后只有有限的恢复可能，因此在疾病进展的早期阶段预防轴突退化对于预防AD是必要的。远志（PR）是一种用于镇静和治疗失忆的传统草药。在本研究中，我们旨在阐明并分析PR对转基因AD小鼠模型5XFAD中记忆缺陷的预防作用。5XFAD小鼠在5个月大时表现出记忆缺陷。因此，将远志水提取物（PR提取物）口服给予4个月大且未表现出记忆障碍迹象的5XFAD小鼠。连续给药56天后，PR提取物预防了5XFAD小鼠鼻周皮质中与淀粉样β（Aβ）斑块积累相关的认知缺陷和轴突退化。PR提取物不影响5XFAD小鼠脑中Aβ斑块的形成。在培养的神经元中，PR提取物预防了由Aβ诱导的轴突生长锥塌陷和轴突萎缩。此外，它还预防了Aβ诱导的培养神经元生长锥处的内吞作用。我们之前的研究报道，抑制内吞作用足以预防Aβ诱导的生长锥塌陷、轴突退化和记忆障碍。因此，PR提取物可能通过抑制内吞作用预防了轴突退化和记忆障碍。PR是第一种用于AD的通过抑制神经元内吞作用发挥预防作用的候选药物。
