Leung Emily, Hazrati Lili-Naz
Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 Kings College Cir, Toronto, ON M5S 1A8, Canada.
The Hospital for Sick Children, 555 University Ave, Toronto, ON M5G 1X8, Canada.
Brain Commun. 2021 May 27;3(2):fcab117. doi: 10.1093/braincomms/fcab117. eCollection 2021.
Numerous cellular processes, including toxic protein aggregation and oxidative stress, have been studied extensively as potential mechanisms underlying neurodegeneration. However, limited therapeutic efficacy targeting these processes has prompted other mechanisms to be explored. Previous research has emphasized a link between cellular senescence and neurodegeneration, where senescence induced by excess DNA damage and deficient DNA repair results in structural and functional changes that ultimately contribute to brain dysfunction and increased vulnerability for neurodegeneration. Specific DNA repair proteins, such as breast cancer type 1, have been associated with both stress-induced senescence and neurodegenerative diseases, however, specific mechanisms remain unclear. Therefore, this review explores DNA damage-induced senescence in the brain as a driver of neurodegeneration, with particular focus on breast cancer type 1, and its potential contribution to sex-specific differences associated with neurodegenerative disease.
许多细胞过程，包括有毒蛋白质聚集和氧化应激，作为神经退行性变的潜在机制已被广泛研究。然而，针对这些过程的治疗效果有限，促使人们探索其他机制。先前的研究强调了细胞衰老与神经退行性变之间的联系，其中过量DNA损伤和DNA修复缺陷诱导的衰老导致结构和功能变化，最终导致脑功能障碍和神经退行性变易感性增加。特定的DNA修复蛋白，如乳腺癌1型，已与应激诱导的衰老和神经退行性疾病相关联，然而，具体机制仍不清楚。因此，本综述探讨大脑中DNA损伤诱导的衰老作为神经退行性变的驱动因素，特别关注乳腺癌1型，及其对神经退行性疾病相关性别差异的潜在影响。
