Section of Neuromedical Science, Institute of Natural Medicine, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan.
Laboratory of Pharmacognosy, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511, Japan.
Int J Mol Sci. 2020 Jun 30;21(13):4665. doi: 10.3390/ijms21134665.
In Alzheimer's disease (AD), amyloid β (Aβ) induces axonal degeneration, neuronal network disruption, and memory impairment. Although many candidate drugs to reduce Aβ have been clinically investigated, they failed to recover the memory function in AD patients. Reportedly, Aβ deposition occurred before the onset of AD. Once neuronal networks were disrupted by Aβ, they could hardly be recovered. Therefore, we speculated that only removal of Aβ was not enough for AD therapy, and prevention and recovery from neuronal network disruption were also needed. This review describes the challenges related to the condition of axons for AD therapy. We established novel in vitro models of Aβ-induced axonal degeneration. Using these models, we found that several traditional medicines and their constituents prevented or helped recover from Aβ-induced axonal degeneration. These drugs also prevented or helped recover from memory impairment in in vivo models of AD. One of these drugs ameliorated memory decline in AD patients in a clinical study. These results indicate that prevention and recovery from axonal degeneration are possible strategies for AD therapy.
在阿尔茨海默病（AD）中，淀粉样蛋白β（Aβ）可诱导轴突变性、神经元网络破坏和记忆损伤。尽管已有许多候选药物被用于临床研究以减少 Aβ，但它们均未能恢复 AD 患者的记忆功能。据报道，Aβ沉积发生在 AD 发病之前。一旦神经元网络被 Aβ破坏，就很难恢复。因此，我们推测，仅去除 Aβ对于 AD 治疗来说是不够的，还需要预防和恢复神经元网络的破坏。本综述描述了与 AD 治疗相关的轴突状况的挑战。我们建立了新型 Aβ诱导的轴突变性体外模型。使用这些模型，我们发现几种传统药物及其成分可预防或有助于恢复 Aβ诱导的轴突变性。这些药物还可预防或有助于恢复 AD 动物模型中的记忆障碍。其中一种药物在一项 AD 患者的临床研究中改善了记忆下降。这些结果表明，预防和恢复轴突变性是 AD 治疗的一种可能策略。
