TDP-43 proteinopathy in frontotemporal lobar degeneration and amyotrophic lateral sclerosis: From pathomechanisms to therapeutic strategies.
Ageing Res Rev
; 100: 102441, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-39069095
ABSTRACT
Proteostasis failure is a common pathological characteristic in neurodegenerative diseases. Revitalizing clearance systems could effectively mitigate these diseases. The transactivation response (TAR) DNA-binding protein 43 (TDP-43) plays a critical role as an RNA/DNA-binding protein in RNA metabolism and synaptic function. Accumulation of TDP-43 aggregates in the central nervous system is a hallmark of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Autophagy, a major and highly conserved degradation pathway, holds the potential for degrading aggregated TDP-43 and alleviating FTLD/ALS. This review explores the causes of TDP-43 aggregation, FTLD/ALS-related genes, key autophagy factors, and autophagy-based therapeutic strategies targeting TDP-43 proteinopathy. Understanding the underlying pathological mechanisms of TDP-43 proteinopathy can facilitate therapeutic interventions.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA-Binding Proteins
/
Frontotemporal Lobar Degeneration
/
TDP-43 Proteinopathies
/
Amyotrophic Lateral Sclerosis
Limits:
Animals
/
Humans
Language:
En
Journal:
Ageing Res Rev
Journal subject:
GERIATRIA
Year:
2024
Document type:
Article
Country of publication:
Reino Unido