Therapeutic Potential Effect of Glycogen Synthase Kinase 3 Beta (GSK-3β) Inhibitors in Parkinson Disease: Exploring an Overlooked Avenue.

GSK-3β Parkinson’s disease

Journal

Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963

Informations de publication

Date de publication:
17 Feb 2024
Historique:
received: 24 09 2023
accepted: 20 01 2024
medline: 17 2 2024
pubmed: 17 2 2024
entrez: 17 2 2024
Statut: aheadofprint

Résumé

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-3β) is implicated in the pathogenesis of PD. Therefore, the purpose of the present review was to revise the mechanistic role of GSK-3β in PD neuropathology, and how GSK-3β 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-3β is also interconnected with the development of different neurodegenerative diseases. However, the underlying mechanism of GSK-3β in PD neuropathology is not fully clarified. Over-expression of GSK-3β 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-3β in PD leading to progressive neuronal injury. Higher expression of GSK-3β in the early stages of PD neuropathology might contribute to the reduction of neuroprotective brain-derived neurotrophic factor (BDNF). Thus, GSK-3β inhibitors may be effective in PD by reducing inflammatory and oxidative stress disorders which are associated with degeneration of dopaminergic in the SN.

Identifiants

pubmed: 38367137
doi: 10.1007/s12035-024-04003-z
pii: 10.1007/s12035-024-04003-z
doi:

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s).

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Auteurs

Areej Turkistani (A)

Department of Pharmacology and Toxicology, College of Medicine, Taif University, 21944, Taif, Saudi Arabia.

Hayder M Al-Kuraishy (HM)

Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, P.O. Box 14132, Baghdad, Iraq.

Ali I Al-Gareeb (AI)

Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, P.O. Box 14132, Baghdad, Iraq.

Ali K Albuhadily (AK)

Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, P.O. Box 14132, Baghdad, Iraq.

Athanasios Alexiou (A)

University Centre for Research & Development, Chandigarh University, Chandigarh-Ludhiana Highway, Mohali, Punjab, India.
Department of Research & Development, Funogen, Athens, Greece.
Department of Research & Development, AFNP Med, 1030, Vienna, Austria.
Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, NSW, 2770, Australia.

Marios Papadakis (M)

Department of Surgery II, University Hospital Witten-Herdecke, Heusnerstrasse 40, University of Witten-Herdecke, 42283, Wuppertal, Germany. drmariospapadakis@gmail.com.

Mohamed M Elfiky (MM)

Anatomy Department, General Medicine Practice Program, Batterjee Medical College, Jeddah, Saudi Arabia.
Anatomy Department, Faculty of Medicine, Menoufia University, Shibin El Kom, Al Minufya, Egypt.

Hebatallah M Saad (HM)

Department of Pathology, Faculty of Veterinary Medicine, Matrouh University, Matrouh, 51744, Egypt.

Gaber El-Saber Batiha (GE)

Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, AlBeheira, Egypt.

Classifications MeSH