衰老、细胞衰老与神经退行性疾病。
Ageing, Cellular Senescence and Neurodegenerative Disease.
机构信息
Laboratory of Histology & Embryology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, Goudi, 115-27 Athens, Greece.
出版信息
Int J Mol Sci. 2018 Sep 27;19(10):2937. doi: 10.3390/ijms19102937.
Ageing is a major risk factor for developing many neurodegenerative diseases. Cellular senescence is a homeostatic biological process that has a key role in driving ageing. There is evidence that senescent cells accumulate in the nervous system with ageing and neurodegenerative disease and may predispose a person to the appearance of a neurodegenerative condition or may aggravate its course. Research into senescence has long been hindered by its variable and cell-type specific features and the lack of a universal marker to unequivocally detect senescent cells. Recent advances in senescence markers and genetically modified animal models have boosted our knowledge on the role of cellular senescence in ageing and age-related disease. The aim now is to fully elucidate its role in neurodegeneration in order to efficiently and safely exploit cellular senescence as a therapeutic target. Here, we review evidence of cellular senescence in neurons and glial cells and we discuss its putative role in Alzheimer's disease, Parkinson's disease and multiple sclerosis and we provide, for the first time, evidence of senescence in neurons and glia in multiple sclerosis, using the novel GL13 lipofuscin stain as a marker of cellular senescence.
衰老是许多神经退行性疾病发展的主要风险因素。细胞衰老(cellular senescence)是一种维持生物体内平衡的生理过程,它在驱动衰老过程中起着关键作用。有证据表明,衰老细胞会随着年龄的增长和神经退行性疾病在神经系统中积累,并可能使人更容易出现神经退行性疾病,或使其病情恶化。长期以来,由于衰老的特征具有可变性和细胞类型特异性,以及缺乏明确检测衰老细胞的通用标志物,因此对衰老的研究一直受到阻碍。最近,在衰老标志物和基因修饰动物模型方面的进展,提高了我们对细胞衰老在衰老和与年龄相关疾病中的作用的认识。现在的目标是充分阐明其在神经退行性变中的作用,以便有效地、安全地利用细胞衰老作为治疗靶点。在这里,我们回顾了神经元和神经胶质细胞中细胞衰老的证据,并讨论了其在阿尔茨海默病、帕金森病和多发性硬化症中的潜在作用,同时还首次使用新型 GL13 脂褐素染色作为细胞衰老的标志物,提供了多发性硬化症中神经元和神经胶质细胞衰老的证据。