TDP-43 post-translational modifications in health and disease

Introduction: Nuclear factor TDP-43 is a ubiquitously expressed RNA binding protein that plays a key causative role in several neurodegenerative diseases, especially in the ALS/FTD spectrum. In addition, its aberrant aggregation and expression has been recently observed in other type of diseases, su...

Full description

Saved in:
Bibliographic Details
Published in:Expert opinion on therapeutic targets Vol. 22; no. 3; pp. 279 - 293
Main Author: Buratti, Emanuele
Format: Journal Article
Language:English
Published: England Taylor & Francis 04.03.2018
Subjects:
ALS
Amyotrophic Lateral Sclerosis - genetics
Amyotrophic Lateral Sclerosis - physiopathology
Amyotrophic Lateral Sclerosis - therapy
Animals
DNA-Binding Proteins - genetics
Down-Regulation
Frontotemporal Lobar Degeneration - genetics
Frontotemporal Lobar Degeneration - physiopathology
Frontotemporal Lobar Degeneration - therapy
FTLD
Gene Expression Regulation
Humans
IBM
Molecular Targeted Therapy
Neurodegenerative Diseases - genetics
Neurodegenerative Diseases - physiopathology
Neurodegenerative Diseases - therapy
NPC
post-translational modifications
Protein Processing, Post-Translational
TDP-43
NPC
ALS
post-translational modifications
IBM
TDP-43
FTLD
ISSN:1472-8222, 1744-7631, 1744-7631
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Introduction: Nuclear factor TDP-43 is a ubiquitously expressed RNA binding protein that plays a key causative role in several neurodegenerative diseases, especially in the ALS/FTD spectrum. In addition, its aberrant aggregation and expression has been recently observed in other type of diseases, such as myopathies and Niemann-Pick C, a lysosomal storage disease. Areas covered: This review aims to specifically cover the post-translational modifications (PTMs) that can affect TDP-43 function and cellular status both in health and disease. To this date, these include phosphorylation, formation of C-terminal fragments, disulfide bridge formation, ubiquitination, acetylation, and sumoylation. Recently published articles on these subjects have been reviewed in this manuscript. Expert opinion: Targeting aberrant TDP-43 expression in neurodegenerative diseases is a very challenging task due to the fact that both its overexpression and downregulation are considerably toxic to cells. This characteristic makes it difficult to therapeutically target this protein in a generalized manner. An alternative approach could be the identification of specific aberrant PTMs that promote its aggregation or toxicity, and developing novel therapeutic approaches toward their selective modification.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
ObjectType-Review-3
content type line 23
ISSN:1472-8222
1744-7631
1744-7631
DOI:10.1080/14728222.2018.1439923