Notch 信号通路在神经血管衰老和阿尔茨海默病中的作用。
Role of Notch signaling in neurovascular aging and Alzheimer's disease.
机构信息
Department of Psychological Science, University of California, Irvine, Irvine, CA, USA.
Department of Psychological Science, University of California, Irvine, Irvine, CA, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
出版信息
Semin Cell Dev Biol. 2021 Aug;116:90-97. doi: 10.1016/j.semcdb.2020.12.011. Epub 2020 Dec 28.
The Notch signaling pathway is an evolutionarily conserved cell signaling system known to be involved in vascular development and function. Recent evidence suggests that dysfunctional Notch signaling could play a critical role in the pathophysiology of neurodegenerative diseases. We reviewed current literature on the role of Notch signaling pathway, and specifically Notch receptor genes and proteins, in aging, cerebrovascular disease and Alzheimer's disease. We hypothesize that Notch signaling may represent a key point of overlap between age-related vascular and Alzheimer's pathophysiology contributing to their comorbidity and combined influence on cognitive decline and dementia. Numerous findings from studies of genetics, neuropathology and cell culture models all suggest a link between altered Notch signaling and Alzheimer's pathophysiology. Age-related changes in Notch signaling may also trigger neurovascular dysfunction, contributing to the development of neurodegenerative diseases; however, additional studies are warranted. Future research directly exploring the influence of aberrant Notch signaling in the development of Alzheimer's disease is needed to better understand this mechanism.
Notch 信号通路是一种进化上保守的细胞信号系统，已知参与血管发育和功能。最近的证据表明，功能失调的 Notch 信号可能在神经退行性疾病的病理生理学中发挥关键作用。我们回顾了 Notch 信号通路、特别是 Notch 受体基因和蛋白在衰老、脑血管疾病和阿尔茨海默病中的作用的现有文献。我们假设 Notch 信号可能代表与年龄相关的血管和阿尔茨海默病病理生理学之间的一个关键重叠点，导致它们的共病和对认知能力下降和痴呆的共同影响。遗传学、神经病理学和细胞培养模型研究的大量发现都表明 Notch 信号的改变与阿尔茨海默病的病理生理学之间存在联系。Notch 信号的年龄相关变化也可能引发神经血管功能障碍，导致神经退行性疾病的发生；然而，还需要更多的研究。需要进行直接探索异常 Notch 信号在阿尔茨海默病发展中的作用的未来研究，以更好地理解这一机制。
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