Therapeutic Potential Effect of Glycogen Synthase Kinase 3 Beta (GSK-3ß) Inhibitors in Parkinson Disease: Exploring an Overlooked Avenue.
Mol Neurobiol
; 61(9): 7092-7108, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-38367137
ABSTRACT
Parkinson's disease (PD) is a progressive neurodegenerative disease of the brain due to degeneration of dopaminergic neurons in the substantia nigra (SN). Glycogen synthase kinase 3 beta (GSK-3ß) is implicated in the pathogenesis of PD. Therefore, the purpose of the present review was to revise the mechanistic role of GSK-3ß in PD neuropathology, and how GSK-3ß inhibitors affect PD neuropathology. GSK-3 is a conserved threonine/serine kinase protein that is intricate in the regulation of cellular anabolic and catabolic pathways by modulating glycogen synthase. Over-expression of GSK-3ß is also interconnected with the development of different neurodegenerative diseases. However, the underlying mechanism of GSK-3ß in PD neuropathology is not fully clarified. Over-expression of GSK-3ß induces the development of PD by triggering mitochondrial dysfunction and oxidative stress in the dopaminergic neurons of the SN. NF-κB and NLRP3 inflammasome are activated in response to dysregulated GSK-3ß in PD leading to progressive neuronal injury. Higher expression of GSK-3ß in the early stages of PD neuropathology might contribute to the reduction of neuroprotective brain-derived neurotrophic factor (BDNF). Thus, GSK-3ß inhibitors may be effective in PD by reducing inflammatory and oxidative stress disorders which are associated with degeneration of dopaminergic in the SN.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
/
Glucógeno Sintasa Quinasa 3 beta
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Neurobiol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Arabia Saudita