Spreading of TDP-43 pathology via pyramidal tract induces ALS-like phenotypes in TDP-43 transgenic mice.
Acta Neuropathol Commun
; 9(1): 15, 2021 01 18.
Article
em En
| MEDLINE
| ID: mdl-33461623
ABSTRACT
Transactive response DNA-binding protein 43 kDa (TDP-43) has been identified as the major component of ubiquitinated inclusions found in patients with sporadic amyotrophic lateral sclerosis (ALS). Increasing evidence suggests prion-like transmission of TDP-43 aggregates via neuroanatomic connection in vitro and pyramidal tract in vivo. However, it is still unknown whether the spreading of pathological TDP-43 sequentially via pyramidal tract can initiate ALS-like pathology and phenotypes. In this study, we reported that injection of TDP-43 preformed fibrils (PFFs) into the primary motor cortex (M1) of Thy1-e (IRES-TARDBP) 1 mice induced the spreading of pathological TDP-43 along pyramidal tract axons anterogradely. Moreover, TDP-43 PFFs-injected Thy1-e (IRES-TARDBP) 1 mice displayed ALS-like neuropathological features and symptoms, including motor dysfunctions and electrophysiological abnormalities. These findings provide direct evidence that transmission of pathological TDP-43 along pyramidal tract induces ALS-like phenotypes, which further suggest the potential mechanism for TDP-43 proteinopathy.
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Assunto principal:
Tratos Piramidais
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Transporte Axonal
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Proteínas de Ligação a DNA
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Agregação Patológica de Proteínas
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Agregados Proteicos
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Esclerose Lateral Amiotrófica
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Córtex Motor
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article