Altmeyer Matthias, Hottiger Michael O
Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Zurich, Switzerland.
Aging (Albany NY). 2009 May 20;1(5):458-69. doi: 10.18632/aging.100052.
Poly(ADP-ribose) polymerase 1 (PARP1) is a chromatin-associated nuclear protein, which functions as molecular stress sensor. Reactive oxygen species, responsible for the most plausible and currently acceptable global mechanism to explain the aging process, strongly activate the enzymatic activity of PARP1 and the formation of poly(ADP-ribose) (PAR) from NAD(+). Consumption of NAD(+) links PARP1 to energy metabolism and to a large number of NAD(+)-dependent enzymes, such as the sirtuins. As transcriptional cofactor for NF-kappaB-dependent gene expression, PARP1 is also connected to the immune response, which is implicated in almost all age-related or associated diseases. Accordingly, numerous experimental studies have demonstrated the beneficial effects of PARP inhibition for several age-related diseases. This review summarizes recent findings on PARP1 and puts them in the context of metabolic stress and inflammation in aging.
聚（ADP - 核糖）聚合酶1（PARP1）是一种与染色质相关的核蛋白，作为分子应激传感器发挥作用。活性氧是解释衰老过程最合理且目前被广泛接受的整体机制的关键因素，它能强烈激活PARP1的酶活性，并促使NAD⁺形成聚（ADP - 核糖）（PAR）。NAD⁺的消耗将PARP1与能量代谢以及大量依赖NAD⁺的酶（如沉默调节蛋白）联系起来。作为NF - κB依赖性基因表达的转录辅因子，PARP1还与免疫反应相关，而免疫反应几乎涉及所有与年龄相关或相关的疾病。因此，众多实验研究已证明PARP抑制对多种与年龄相关疾病具有有益作用。本综述总结了关于PARP1的最新研究发现，并将其置于衰老过程中的代谢应激和炎症背景下进行探讨。
