细胞死亡通路帕塔那托斯与视网膜疾病的关系
Parthanatos as a Cell Death Pathway Underlying Retinal Disease.
机构信息
Ocular Genomics Institute, Department of Ophthalmology, Massachusetts Eye & Ear, Harvard Medical School, Boston, MA, USA.
出版信息
Adv Exp Med Biol. 2019;1185:323-327. doi: 10.1007/978-3-030-27378-1_53.
Abstract
Parthanatos is a programmed cell death pathway mediated by the effects of pathogenically high levels of poly(ADP-ribose) polymerase 1 (PARP1) activity. This process underlies a broad range of diseases affecting many tissues and organs across the body, including the retina. This chapter reviews mechanisms that are currently understood to drive parthanatos in the context of retinal diseases associated with this form of cell death. Toxicity of upregulated poly(ADP-ribose) (PAR) content, NAD and ATP depletion, translocation of apoptosis-inducing factor (AIF) to the nucleus, and loss of glycolytic function are discussed. Since therapies that preserve vulnerable cells remain elusive for the vast majority of retinal diseases, pharmacologically blocking parthanatos may be an effective treatment strategy for cases in which this process contributes to pathogenesis.
摘要
细胞坏死性凋亡是一种由聚（ADP-核糖）聚合酶 1（PARP1）活性过高引起的细胞程序性死亡途径。该过程是许多影响全身许多组织和器官的疾病的基础，包括视网膜。本章综述了目前已知的在与这种细胞死亡形式相关的视网膜疾病中导致细胞坏死性凋亡的机制。讨论了上调的聚（ADP-核糖）（PAR）含量、NAD 和 ATP 耗竭、凋亡诱导因子（AIF）向核内易位以及糖酵解功能丧失的毒性。由于对于绝大多数视网膜疾病而言，保留脆弱细胞的治疗方法仍然难以捉摸，因此在这种过程导致发病机制的情况下，药理学上阻断细胞坏死性凋亡可能是一种有效的治疗策略。
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