Portal de investigación
Neuroprotective Effect of IND1316, an Indole-Based AMPK Activator, in Animal Models of Huntington Disease.
Fecha de publicación:
Fecha Ahead of Print:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Vela, Marta
- Garcia-Gimeno, Maria Adelaida
- Cumella, Jose
- Lagartera, Laura
- Perez, Concepcion
- Priego, Eva-Maria
- Campos, Angela
- Sanz, Pascual
- Castro, Ana
Grupos
Abstract
Aggregation of mutant huntingtin, because of an expanded polyglutamine track, underlies the cause of neurodegeneration in Huntington disease (HD). However, it remains unclear how some alterations at the cellular level lead to specific structural changes in HD brains. In this context, the neuroprotective effect of the activation of AMP-activated protein kinase (AMPK) appears to be a determinant factor in several neurodegenerative diseases, including HD. In the present work, we describe a series of indole-derived compounds able to activate AMPK at the cellular level. By using animal models of HD (both worms and mice), we demonstrate the in vivo efficacy of one of these compounds (IND1316), confirming that it can reduce the neuropathological symptoms of this disease. Taken together, in vivo results and in silico studies of druggability, allow us to suggest that IND1316 could be considered as a promising new lead compound for the treatment of HD and other central nervous system diseases in which the activation of AMPK results in neuroprotection.
Datos de la publicación
- ISSN/ISSNe:
- 1948-7193, 1948-7193
- Tipo:
- Article
- Páginas:
- 275-287
- PubMed:
- 34962383
- Factor de Impacto:
- 1,140 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
ACS Chemical Neuroscience AMER CHEMICAL SOC
Citas Recibidas en Web of Science: 9
Documentos
- No hay documentos
Filiaciones
Keywords
- *ADME in silico; *AMPK; *C. elegans models; *Huntington disease mouse models; *indole derivatives; *neuroprotection; *polyQ toxicity
Cita
Vela M,Garcia MA,SANCHIS A,BONO J,Cumella J,Lagartera L,Perez C,Priego E,Campos A,Sanz P,VAZQUEZ RP,Castro A. Neuroprotective Effect of IND1316, an Indole-Based AMPK Activator, in Animal Models of Huntington Disease. ACS Chem. Neurosci. 2022. 13. (2):p. 275-287. IF:5,000. (2).