New insights of poly(ADP-ribosylation) in neurodegenerative diseases: A focus on protein phase separation and pathologic aggregation.
PARP
Phase separation
TDP-43
hnRNP A1
α-Synuclein
Journal
Biochemical pharmacology
ISSN: 1873-2968
Titre abrégé: Biochem Pharmacol
Pays: England
ID NLM: 0101032
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
29
03
2019
accepted:
25
04
2019
pubmed:
30
4
2019
medline:
31
3
2020
entrez:
30
4
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31034795
pii: S0006-2952(19)30163-7
doi: 10.1016/j.bcp.2019.04.028
pii:
doi:
Substances chimiques
Poly(ADP-ribose) Polymerase Inhibitors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
58-63Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.