TDP-43 proteinopathy in frontotemporal lobar degeneration and amyotrophic lateral sclerosis: From pathomechanisms to therapeutic strategies.

Autor: Ho PC; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan., Hsieh TC; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan., Tsai KJ; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Research Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address: kjtsai@mail.ncku.edu.tw.
Jazyk: angličtina
Zdroj: Ageing research reviews [Ageing Res Rev] 2024 Sep; Vol. 100, pp. 102441. Date of Electronic Publication: 2024 Jul 27.
DOI: 10.1016/j.arr.2024.102441
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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