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

Autor: Turkistani A; Department of Pharmacology and Toxicology, College of Medicine, Taif University, 21944, Taif, Saudi Arabia., Al-Kuraishy HM; Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, P.O. Box 14132, Baghdad, Iraq., Al-Gareeb AI; Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, P.O. Box 14132, Baghdad, Iraq., Albuhadily AK; Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, P.O. Box 14132, Baghdad, Iraq., 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., Papadakis M; Department of Surgery II, University Hospital Witten-Herdecke, Heusnerstrasse 40, University of Witten-Herdecke, 42283, Wuppertal, Germany. drmariospapadakis@gmail.com., 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., Saad HM; Department of Pathology, Faculty of Veterinary Medicine, Matrouh University, Matrouh, 51744, Egypt., Batiha GE; Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, AlBeheira, Egypt.
Jazyk: angličtina
Zdroj: Molecular neurobiology [Mol Neurobiol] 2024 Sep; Vol. 61 (9), pp. 7092-7108. Date of Electronic Publication: 2024 Feb 17.
DOI: 10.1007/s12035-024-04003-z
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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