期刊
BIOCHEMICAL PHARMACOLOGY
卷 167, 期 -, 页码 58-63出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2019.04.028
关键词
alpha-Synuclein; hnRNP A1; TDP-43; Phase separation; PARP
资金
- National Key R&D Program of China [2016YFA0501902]
- National Natural Science Foundation of China [81671254, 31471017, 91853112, 31470748]
Abnormal protein aggregation is a common pathological feature of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). Protein posttranslational modifications (PTMs) play a crucial regulatory role in the formation of pathologic aggregation. Among the known PTMs involved in neurodegeneration, poly(ADP-ribosylation) (PARylation) has emerged with promising therapeutic potentials of the use of poly(ADP-ribose) (PAR) polymerase (PARP) inhibitors. In this review, we describe the mounting evidence that abnormal PARP activation is involved in various neurodegenerative diseases, and discuss the underpinning mechanisms with a focus on the recent findings that PARylation affects liquid-liquid phase separation and aggregation of amyloid proteins. We hope this review will stimulate further investigation of the unknown functions of PARylation and promote the development of more effective therapeutic agents in treating neurodegeneration.
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