Department of Pharmacology, University of Virginia, Charlottesville, VA, USA.
Department of Biology, University of Virginia, Charlottesville, VA, USA.
J Alzheimers Dis. 2019;67(1):1-11. doi: 10.3233/JAD-180874.
Aberrant neuronal cell cycle re-entry (CCR) is a phenomenon that precedes and may mechanistically lead to a majority of the neuronal loss observed in Alzheimer's disease (AD). Recent developments concerning the regulation of aberrant neuronal CCR in AD suggest that there are potential intracellular signaling "hotspots" in AD, cancer, and brain insulin resistance, the latter of which is characteristically associated with AD. Critically, these common signaling nodes across different human diseases may represent currently untapped therapeutic opportunities for AD. Specifically, repurposing of existing US Food and Drug Administration-approved pharmacological agents, including experimental therapeutics that target the cell cycle in cancer, may be an innovative avenue for future AD-directed drug discovery and development. In this review we discuss overlapping aspects of AD, cancer, and brain insulin resistance from the perspective of neuronal CCR, and consider strategies to exploit them for prevention or therapeutic intervention of AD.
异常的神经元细胞周期再进入（CCR）是一种先于并可能在机制上导致阿尔茨海默病（AD）中观察到的大多数神经元丢失的现象。最近关于 AD 中异常神经元 CCR 的调节的研究进展表明，AD、癌症和大脑胰岛素抵抗中存在潜在的细胞内信号“热点”，后者与 AD 密切相关。关键的是，这些不同人类疾病之间的共同信号节点可能代表着目前针对 AD 尚未开发的治疗机会。具体来说，重新利用现有的美国食品和药物管理局批准的药理学制剂，包括针对癌症细胞周期的实验性治疗药物，可能是未来针对 AD 的药物发现和开发的创新途径。在这篇综述中，我们从神经元 CCR 的角度讨论了 AD、癌症和大脑胰岛素抵抗的重叠方面，并考虑了利用这些方面预防或治疗 AD 的策略。
