Zhang Hua, Bezprozvanny Ilya
Department of Physiology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Laboratory of Molecular Neurodegeneration, Peter the Great St. Petersburg State Polytechnical University, St. Petersburg 195251, Russia.
Life (Basel). 2023 May 15;13(5):1187. doi: 10.3390/life13051187.
Alzheimer's disease (AD) is the most common cause of dementia. There is a growing body of evidence that dysregulation in neuronal calcium (Ca) signaling plays a major role in the initiation of AD pathogenesis. In particular, it is well established that Ryanodine receptor (RyanR) expression levels are increased in AD neurons and Ca release via RyanRs is augmented in AD neurons. Autophagy is important for removing unnecessary or dysfunctional components and long-lived protein aggregates, and autophagy impairment in AD neurons has been extensively reported. In this review we discuss recent results that suggest a causal link between intracellular Ca signaling and lysosomal/autophagic dysregulation. These new results offer novel mechanistic insight into AD pathogenesis and may potentially lead to identification of novel therapeutic targets for treating AD and possibly other neurodegenerative disorders.
阿尔茨海默病（AD）是痴呆最常见的病因。越来越多的证据表明，神经元钙（Ca）信号失调在AD发病机制的起始过程中起主要作用。特别是，已有充分证据表明，AD神经元中兰尼碱受体（RyanR）的表达水平升高，且通过RyanR的Ca释放也在AD神经元中增强。自噬对于清除不必要或功能失调的成分以及长寿蛋白聚集体很重要，并且AD神经元中的自噬损伤已被广泛报道。在本综述中，我们讨论了最近的结果，这些结果表明细胞内Ca信号与溶酶体/自噬失调之间存在因果关系。这些新结果为AD发病机制提供了新的机制性见解，并可能潜在地导致识别出治疗AD以及可能其他神经退行性疾病的新治疗靶点。
