IL-4/STAT6 axis observed to reverse proliferative defect in SCA3 patient-derived neural progenitor cells.
Clin Exp Pharmacol Physiol
; 51(1): 30-39, 2024 01.
Article
en En
| MEDLINE
| ID: mdl-37933553
ABSTRACT
Spinocerebellar ataxia 3 (SCA3) is an incurable, neurodegenerative genetic disorder that leads to progressive cerebellar ataxia and other parkinsonian-like pathologies because of loss of cerebellar neurons. The role of an expanded polyglutamine aggregate on neural progenitor cells is unknown. Here, we show that SCA3 patient-specific induced neural progenitor cells (iNPCs) exhibit proliferative defects. Moreover, SCA3 iNPCs have reduced autophagic expression compared to control. Furthermore, although SCA3 iNPCs continue to proliferate, they do not survive subsequent passages compared to control iNPCs, indicating the likelihood that SCA3 iNPCs undergo rapid senescence. Exposure to interleukin-4 (IL-4), a type 2 cytokine produced by immune cells, resulted in an observed increase in expression of autophagic programs and a reduction in the proliferation defect observed in SCA3 iNPCs. Our results indicate a previously unobserved role of SCA3 disease ontology on the neural stem cell pool and a potential therapeutic strategy using IL-4 to ameliorate or delay disease pathology in the SCA3 neural progenitor cell population.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Machado-Joseph
/
Células-Madre Neurales
Límite:
Humans
Idioma:
En
Revista:
Clin Exp Pharmacol Physiol
Año:
2024
Tipo del documento:
Article
País de afiliación:
China