The role of TDP-43 propagation in neurodegenerative diseases: integrating insights from clinical and experimental studies.
Exp Mol Med
; 52(10): 1652-1662, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-33051572
ABSTRACT
TAR DNA-binding protein 43 (TDP-43) is a highly conserved nuclear RNA/DNA-binding protein involved in the regulation of RNA processing. The accumulation of TDP-43 aggregates in the central nervous system is a common feature of many neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease (AD), and limbic predominant age-related TDP-43 encephalopathy (LATE). Accumulating evidence suggests that prion-like spreading of aberrant protein aggregates composed of tau, amyloid-ß, and α-synuclein is involved in the progression of neurodegenerative diseases such as AD and PD. Similar to those of prion-like proteins, pathological aggregates of TDP-43 can be transferred from cell-to-cell in a seed-dependent and self-templating manner. Here, we review clinical and experimental studies supporting the prion-like spreading of misfolded TDP-43 and discuss the molecular mechanisms underlying the propagation of these pathological aggregated proteins. The idea that misfolded TDP-43 spreads in a prion-like manner between cells may guide novel therapeutic strategies for TDP-43-associated neurodegenerative diseases.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doenças Neurodegenerativas
/
Suscetibilidade a Doenças
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Proteínas de Ligação a DNA
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article