Connecting the Dots: Neuronal Senescence, Stress Granules, and Neurodegeneration.
Connecting the Dots: Neuronal Senescence, Stress Granules, and Neurodegeneration.
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DOI：
10.1016/j.gene.2023.147437
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发表时间：
2023-04
期刊：
影响因子：
3.5
通讯作者：
Yizhe Ma;Natalie G. Farny
中科院分区：
文献类型：
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作者：
Yizhe Ma;Natalie G. Farny
细胞衰老随着年龄的增长而增加。虽然衰老与细胞周期的退出有关，但有充分的证据表明，包括神经元在内的有丝分裂后细胞可以随着大脑老化而经历衰老，并且衰老可能显著促进神经退行性疾病（ND）如阿尔茨海默病（AD）和肌萎缩性侧索硬化症（ALS）的进展。应激颗粒（SG）是应激诱导的细胞质RNA和蛋白质的生物分子缩合物，其与AD和ALS的发展有关。ND的SG播种假说提出，老化神经元中的慢性应激导致静态SG进展为病理性聚集体。SG动力学的改变也与衰老有关，尽管尚未进行在ND和老化大脑的背景下将SG和衰老联系起来的研究。在这篇综述中，我们总结了有关衰老的文献，并探讨了衰老对大脑衰老的贡献。我们描述了衰老神经元和神经胶质细胞的衰老表型，以及它们与神经炎症和AD和ALS发展的联系。我们进一步研究了SGs与衰老和ND的关系。我们提出了一个新的假设，神经元衰老可能有助于SG播种在ND的机制，通过改变SG在老年细胞的动力学，从而提供额外的聚集在老年神经元的机会。
Cellular senescence increases with aging. While senescence is associated with an exit of the cell cycle, there is ample evidence that post-mitotic cells including neurons can undergo senescence as the brain ages, and that senescence likely contributes significantly to the progression of neurodegenerative diseases (ND) such as Alzheimer’s Disease (AD) and Amyotrophic Lateral Sclerosis (ALS). Stress granules (SGs) are stress-induced cytoplasmic biomolecular condensates of RNA and proteins, which have been linked to the development of AD and ALS. The SG seeding hypothesis of NDs proposes that chronic stress in aging neurons results in static SGs that progress into pathological aggregates Alterations in SG dynamics have also been linked to senescence, though studies that link SGs and senescence in the context of NDs and the aging brain have not yet been performed. In this Review, we summarize the literature on senescence, and explore the contribution of senescence to the aging brain. We describe senescence phenotypes in aging neurons and glia, and their links to neuroinflammation and the development of AD and ALS. We further examine the relationships of SGs to senescence and to ND. We propose a new hypothesis that neuronal senescence may contribute to the mechanism of SG seeding in ND by altering SG dynamics in aged cells, thereby providing additional aggregation opportunities within aged neurons.