多腺苷二磷酸核糖基化修饰与神经退行性变性疾病

神经退行性疾病的发病率越来越高，但其治疗手段有限。多腺苷二磷酸核糖基化修饰（PARylation）是由多腺苷二磷酸核糖聚合酶（PARP）催化的蛋白质翻译后修饰。PARylation通过影响蛋白质在细胞内的移位、聚集、蛋白质活性和细胞死亡，参与脑卒中、帕金森病、阿尔茨海默病、运动神经元病等神经退行性变性疾病的发生和发展。PARP抑制剂通过抑制蛋白PARylation，在药物临床前试验和临床试验Ⅰ期都展现了明显的神经保护作用。然而，寻找作用更特异的、符合神经退行性变性疾病治疗药动学特点的新型PARP抑制剂，将是抗神经退行性药物研发的新方向。本文就PARylation与神经退行性变性疾病的研究进展作一综述。

Poly adenosine diphosphate-ribosylation and neurodegenerative diseases

The morbidity of neurodegenerative diseases are increased in recent years, however, the treatment is limited. Poly ADP-ribosylation (PARylation) is a post-translational modification of protein that catalyzed by poly(ADP-ribose) polymerase (PARP). Studies have shown that PARylation is involved in many neurodegenerative diseases such as stroke, Parkinson's diseases, Alzheimer's disease, amyotrophic lateral sclerosis and so on, by affecting intracellular translocation of protein molecules, protein aggregation, protein activity, and cell death. PARP inhibitors have showed neuroprotective efficacy for neurodegenerative diseases in pre-clinical studies and phase Ⅰ clinical trials. To find new PARP inhibitors with more specific effects and specific pharmacokinetic characteristics will be the new direction for the treatment of neurodegenerative diseases. This paper reviews the recent progress on PARylation in neurodegenerative diseases.