Potential therapeutic role of fibroblast growth factor 21 in neurodegeneration: Evidence for ameliorating parkinsonism via silent information regulator 2 homolog 1 and implication for gene therapy.
Neuropharmacology
; 181: 108335, 2020 12 15.
Article
en En
| MEDLINE
| ID: mdl-32979381
ABSTRACT
Parkinson's disease (PD) is one of the common complex neurodegenerative diseases and characterized by abnormal metabolic brain networks. Fibroblast growth factor 21 (FGF21), an endocrine hormone that belongs to the fibroblast growth factor superfamily, plays an extensive role in the regulation of metabolism. However, our understandings of the specific function and mechanisms of FGF21 on PD are still quite limited. Here we aimed to elucidate the actions and the underlying mechanisms of FGF21 on dopaminergic neurodegeneration using cellular and animal models of parkinsonism. To investigate the effects of FGF21 on dopaminergic neurodegeneration in vivo and in vitro, 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine models of PD were utilized, and animals were treated with recombinant FGF21 protein or FGF21 gene delivered via an adeno-associated virus. In the present study, systemic and continuous intracerebroventricular recombinant FGF21 protein administration to mice both prevented behavioral deficits, protected dopaminergic neurons against degeneration, and ameliorated α-synuclein pathology in PD models; and in vivo gene delivery of FGF21 improved PD-like symptoms and pathologies suggesting a potential implication of FGF21 in gene therapy for PD. In vitro evidence confirmed FGF21 mediated neuroprotective benefits against PD pathologies. Further, our data suggested that enhanced autophagy was involved in the FGF21 neuroprotection in PD models, and silent information regulator 2 homolog 1 may play a crucial role in molecular mechanisms underlying anti-PD activities of FGF21.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson Secundaria
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Terapia Genética
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Enfermedades Neurodegenerativas
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Sirtuina 1
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Factores de Crecimiento de Fibroblastos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Neuropharmacology
Año:
2020
Tipo del documento:
Article