Ageing, Cellular Senescence and Neurodegenerative Disease

被引:312
作者
Kritsilis, Marios [1 ]
Rizou, Sophia V. [1 ]
Koutsoudaki, Paraskevi N. [1 ]
Evangelou, Konstantinos [1 ]
Gorgoulis, Vassilis G. [1 ]
Papadopoulos, Dimitrios [1 ]
机构
[1] Univ Athens, Lab Histol & Embryol, Sch Med, 75 Mikras Asias St, Athens 11527, Greece
关键词
neurodegeneration; cellular senescence; ageing; Alzheimer's disease; multiple sclerosis; Parkinson's disease; lipofuscin; SenTraGor(TM) (GL13); senolytics; DEPENDENT KINASE INHIBITORS; STIMULATED PLATELET ACTIVATION; PERIPHERAL-BLOOD LYMPHOCYTES; MILD COGNITIVE IMPAIRMENT; ONSET ALZHEIMERS-DISEASE; TRANSGENIC MOUSE MODEL; BH3 MIMETIC ABT-737; DNA-DAMAGE RESPONSE; MULTIPLE-SCLEROSIS; PARKINSONS-DISEASE;
D O I
10.3390/ijms19102937
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:37
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