Buck Institute for Research on Aging, Novato, CA 94945, USA.
Free Radic Biol Med. 2019 Apr;134:695-701. doi: 10.1016/j.freeradbiomed.2019.01.012. Epub 2019 Jan 9.
Oxidative stress has long been considered a key component contributing to pathologies associated with brain aging and age-related neurodegenerative diseases. The proposed mechanisms involved are varied, but recently have been suggested to include induction of cellular senescence, a cellular growth arrest state characterized by the secretion of pre-inflammatory senescence-associated secretory phenotype (SASP) factors. The post-mitotic status of neurons has been traditionally considered to prohibit cellular senescence, however recent studies have provided compelling evidence that neurons may be capable of undergoing senescence in response to oxidative stress and other factors. Development of senolytics, small molecules that selectively induce senescent cell death, could represent a paradigm change for the treatment of neurodegenerative diseases including Alzheimer's and Parkinson's disease (AD, PD). However, their use depends on unequivocal validation that neurons can senesce and that they do not have detrimental off-target effects in other cell types in the brain and elsewhere.
氧化应激一直被认为是导致与大脑衰老和与年龄相关的神经退行性疾病相关的病理学的关键组成部分。所涉及的提出的机制是多种多样的，但最近有人提出包括诱导细胞衰老，这是一种细胞生长停滞状态，其特征是前炎症衰老相关分泌表型（SASP）因子的分泌。神经元的有丝分裂后状态传统上被认为是禁止细胞衰老的，但是最近的研究提供了令人信服的证据表明，神经元可能能够对氧化应激和其他因素发生衰老。衰老抑制剂的发展，即选择性诱导衰老细胞死亡的小分子，可能代表治疗神经退行性疾病（包括阿尔茨海默病和帕金森病（AD，PD））的治疗范式的改变。然而，它们的使用取决于明确的验证，即神经元可以衰老，并且它们在大脑和其他地方的其他细胞类型中没有有害的脱靶效应。
