细胞衰老在神经退行性疾病中的作用
Yating Wang1, Kamil Kuca2,3,4, Li You5
1College of Life Science, Yangtze University, Jingzhou, 434025, China.
Archives of toxicology
|May 14, 2024
概括
细胞衰老,标志着特定蛋白质表达和分泌,驱动神经退行性疾病 (NDs). 向衰老细胞及其有害分泌物为阿尔茨海默氏症和帕金森病等疾病提供了一个有希望的治疗策略.
科学领域:
- 神经生物学 神经生物学 神经生物学
- 细胞生物学 细胞生物学
- 衰老研究研究 衰老研究
背景情况:
- 细胞衰老越来越多地与神经退行性疾病 (NDs) 的病原发生有关,包括阿尔茨海默氏症和帕金森病.
- 衰老细胞释放与衰老相关的分泌表型 (SASP),可以损害神经细胞,如微质细胞.
- 在ND模型中观察到衰老的标志,包括p16,p21表达和升高的β-galactosidase活性,并导致标志性病理.
研究的目的:
- 阐明细胞衰老有助于神经退行性疾病病原的机制.
- 审查目前针对衰老细胞及其相关途径的策略,以获得ND的治疗益处.
主要方法:
- 关于细胞衰老和神经退行现有文献的综述.
- 分析SASP组件 (例如,MMP-3,IL-1α,IL-6,IL-8) 在神经损伤中的作用.
- 在ND模型中调查衰老特征 (p16,p21,β-galactosidase).
- 针对衰老细胞和信号通路的治疗干预措施的检查 (p38/MAPK,NF-κB).
- 评估端粒缩短作为生物标志物及其与衰老引起的炎症的联系.
主要成果:
- 细胞衰老和SASP有助于β-粉样蛋白和tau病理.
- 在AD模型中,抑制p38/MAPK和NF-κB信号通路,以及衰老细胞清除,减少病理并改善认知.
- 端粒功能障碍会诱导衰老和炎症性细胞因子的释放 (IL-6,TNF-α,IL-1β).
- 端粒酶激活可以防止衰老,并产生神经保护作用.
结论:
- 细胞衰老是神经退行性疾病病理学的重要驱动因素.
- 向衰老细胞,调节SASP和激活端粒酶代表了ND的可行的治疗策略.
- 对老化疗法和端粒维护的进一步研究对治疗阿尔茨海默病,帕金森病和相关疾病充满希望.
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