Institute for Communicative and Cognitive Neurosciences (ICCONS), Palakkad, Kerala, India.
Institute for Communicative and Cognitive Neurosciences (ICCONS), Palakkad, Kerala, India.
Adv Clin Chem. 2019;90:81-132. doi: 10.1016/bs.acc.2019.01.003. Epub 2019 Feb 21.
Ever since their discovery, the telomeres and the telomerase have been topics of intensive research, first as a mechanism of cellular aging and later as an indicator of health and diseases in humans. By protecting the chromosome ends, the telomeres play a vital role in preserving the information in our genome. Telomeres shorten with age and the rate of telomere erosion provides insight into the proliferation history of cells. The pace of telomere attrition is known to increase at the onset of several pathological conditions. Telomere shortening has been emerging as a potential contributor in the pathogenesis of several neurological disorders including autism spectrum disorders (ASD), schizophrenia, Alzheimer's disease (AD), Parkinson's disease (PD) and depression. The rate of telomere attrition in the brain is slower than that of other tissues owing to the low rate of cell proliferation in brain. Telomere maintenance is crucial for the functioning of stem cells in brain. Taking together the studies on telomere attrition in various neurological disorders, an association between telomere shortening and disease status has been demonstrated in schizophrenia, AD and depression, in spite of a few negative reports. But, studies in ASD and PD have failed to produce conclusive results. The cause-effect relationship between TL and neurological disorders is yet to be elucidated. The factors responsible for telomere erosion, which have also been implicated in the pathogenesis of neurological disorders, need to be explored in detail. Telomerase activation is now being considered as a potential therapeutic strategy for neurological disorders.
自发现以来,端粒和端粒酶一直是密集研究的课题,最初是作为细胞衰老的机制,后来又作为人类健康和疾病的指标。端粒通过保护染色体末端,在保护我们基因组中的信息方面发挥着至关重要的作用。端粒随着年龄的增长而缩短,端粒侵蚀的速度提供了对细胞增殖历史的深入了解。已知在几种病理状况开始时,端粒损耗的速度会增加。端粒缩短已成为几种神经退行性疾病发病机制的潜在因素,包括自闭症谱系障碍(ASD)、精神分裂症、阿尔茨海默病(AD)、帕金森病(PD)和抑郁症。由于大脑中的细胞增殖率较低,大脑中端粒损耗的速度比其他组织慢。端粒维持对于大脑中的干细胞功能至关重要。综合各种神经退行性疾病中端粒损耗的研究,尽管有一些负面报道,但已经证明在精神分裂症、AD 和抑郁症中,端粒缩短与疾病状态之间存在关联。但是,在 ASD 和 PD 中的研究未能得出确凿的结论。TL 与神经退行性疾病之间的因果关系仍有待阐明。负责端粒侵蚀的因素也与神经退行性疾病的发病机制有关,需要详细探索。端粒酶激活现在被认为是治疗神经退行性疾病的潜在策略。