SATB1蛋白的缺失导致细胞衰老 作者: 发布时间:/9/20 13:32:36 美国纪念斯隆凯特琳癌症中心Lorenz Studer和洛克菲勒大学Paul Greengard课题组合作研究发现,SATB1蛋白的缺失导致有丝分裂后多巴胺能神经元的p21依赖性细胞衰老。9月19日,《细胞 干细胞》在线发表了这一研究成果。
SATB1是与帕金森病相关的DNA结合蛋白。研究人员发现SATB1可防止有丝分裂后多巴胺能神经元中的细胞衰老。SATB1的缺失导致人干细胞衍生的多巴胺能神经元和小鼠中的多巴胺神经元中的细胞衰老转录程序的激活。他们在体外和体内观察到多巴胺神经元中细胞衰老是SATB1敲除后的核心表型。此外,他们发现SATB1直接抑制多巴胺能神经元中促衰老因子p21的表达。他们的数据表明多巴胺神经元的衰老是帕金森病病理学的一个促成因素。
据了解,细胞衰老是有丝分裂细胞用于防止不受控制的细胞分裂的机制。随着衰老细胞在组织中持续存在,它们会引起局部炎症并对损害周围细胞,从而导致衰老。通常,神经退行性疾病是衰老的疾病,例如帕金森病。细胞衰老对神经变性的影响仍不清楚。
附:英文原文
Title: Loss of SATB1 Induces p21-Dependent Cellular Senescence in Post-mitotic Dopaminergic Neurons
Author: Markus Riessland, Benjamin Kolisnyk, Tae Wan Kim, Jia Cheng, Jason Ni, Jordan A. Pearson, Emily J. Park, Kevin Dam, Devrim Acehan, Lavoisier S. Ramos-Espiritu, Wei Wang, Jack Zhang, Jae-won Shim, Gabriele Ciceri, Lars Brichta, Lorenz Studer, Paul Greengard
Issue Volume: 19 September
Summary:
Cellular senescence is a mechanism used by mitotic cells to prevent uncontrolled cell division. As senescent cells persist in tissues, they cause local inflammation and are harmful to surrounding cells, contributing to aging. Generally, neurodegenerative diseases, such as Parkinson s, are disorders of aging. The contribution of cellular senescence to neurodegeneration is still unclear. SATB1 is a DNA binding protein associated with Parkinson s disease. We report that SATB1 prevents cellular senescence in post-mitotic dopaminergic neurons. Loss of SATB1 causes activation of a cellular senescence transcriptional program in dopamine neurons both in human stem cell-derived dopaminergic neurons and in mice. We observed phenotypes that are central to cellular senescence in SATB1 knockout dopamine neurons in vitro and in vivo. Moreover, we found that SATB1 directly represses expression of the pro-senescence factor p21 in dopaminergic neurons. Our data implicate senescence of dopamine neurons as a contributing factor in the pathology of Parkinson s disease.
DOI: 10.1016/j.stem..08.013
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期刊信息
Cell Stem Cell:《细胞 干细胞》,创刊于。隶属于细胞出版社,最新IF:21.464
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