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

doi:10.1007/s12035-024-04003-z

Review

. 2024 Feb 17.

doi: 10.1007/s12035-024-04003-z. Online ahead of print.

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

Areej Turkistani^#¹, Hayder M Al-Kuraishy^#², Ali I Al-Gareeb², Ali K Albuhadily², Athanasios Alexiou^{3

4

5

6}, Marios Papadakis⁷, Mohamed M Elfiky^{8

9}, Hebatallah M Saad¹⁰, Gaber El-Saber Batiha¹¹

Affiliations

¹ Department of Pharmacology and Toxicology, College of Medicine, Taif University, 21944, Taif, Saudi Arabia.
² Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, P.O. Box 14132, Baghdad, Iraq.
³ University Centre for Research & Development, Chandigarh University, Chandigarh-Ludhiana Highway, Mohali, Punjab, India.
⁴ Department of Research & Development, Funogen, Athens, Greece.
⁵ Department of Research & Development, AFNP Med, 1030, Vienna, Austria.
⁶ Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, NSW, 2770, Australia.
⁷ Department of Surgery II, University Hospital Witten-Herdecke, Heusnerstrasse 40, University of Witten-Herdecke, 42283, Wuppertal, Germany. drmariospapadakis@gmail.com.
⁸ Anatomy Department, General Medicine Practice Program, Batterjee Medical College, Jeddah, Saudi Arabia.
⁹ Anatomy Department, Faculty of Medicine, Menoufia University, Shibin El Kom, Al Minufya, Egypt.
¹⁰ Department of Pathology, Faculty of Veterinary Medicine, Matrouh University, Matrouh, 51744, Egypt.
¹¹ Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, AlBeheira, Egypt.

^# Contributed equally.

PMID: 38367137
DOI: 10.1007/s12035-024-04003-z

Review

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

Areej Turkistani et al. Mol Neurobiol. 2024.

. 2024 Feb 17.

doi: 10.1007/s12035-024-04003-z. Online ahead of print.

Authors

Affiliations

¹ Department of Pharmacology and Toxicology, College of Medicine, Taif University, 21944, Taif, Saudi Arabia.
² Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, P.O. Box 14132, Baghdad, Iraq.
³ University Centre for Research & Development, Chandigarh University, Chandigarh-Ludhiana Highway, Mohali, Punjab, India.
⁴ Department of Research & Development, Funogen, Athens, Greece.
⁵ Department of Research & Development, AFNP Med, 1030, Vienna, Austria.
⁶ Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, NSW, 2770, Australia.
⁷ Department of Surgery II, University Hospital Witten-Herdecke, Heusnerstrasse 40, University of Witten-Herdecke, 42283, Wuppertal, Germany. drmariospapadakis@gmail.com.
⁸ Anatomy Department, General Medicine Practice Program, Batterjee Medical College, Jeddah, Saudi Arabia.
⁹ Anatomy Department, Faculty of Medicine, Menoufia University, Shibin El Kom, Al Minufya, Egypt.
¹⁰ Department of Pathology, Faculty of Veterinary Medicine, Matrouh University, Matrouh, 51744, Egypt.
¹¹ Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, AlBeheira, Egypt.

^# Contributed equally.

PMID: 38367137
DOI: 10.1007/s12035-024-04003-z

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-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.

Keywords: GSK-3β; Parkinson’s disease.

PubMed Disclaimer

References

1. Al-kuraishy HM, Al-Gareeb AI, Kaushik A, Kujawska M, Ahmed EA, Batiha GES (2023) SARS-COV-2 infection and Parkinson’s disease: possible links and perspectives. J Neurosci Res 101(6):952–975 - PubMed - DOI
1. Al-Kuraishy HM, Jabir MS, Al-Gareeb AI, Albuhadily AK (2023) The conceivable role of prolactin hormone in Parkinson disease: the same goal but with different ways. Ageing Res Rev 91:102075. https://doi.org/10.1016/j.arr.2023.102075 - DOI - PubMed
1. Heras-Garvin A, Stefanova N (2020) From synaptic protein to prion: the long and controversial journey of α-synuclein. Front Synaptic Neurosci 12:584536 - PubMed - PMC - DOI
1. Alrouji M, Al-kuraishy HM, Al-Gareeb AI, Alexiou A, Papadakis M, Jabir MS et al (2023) NF-κB/NLRP3 inflammasome axis and risk of Parkinson’s disease in type 2 diabetes mellitus: a narrative review and new perspective. J Cell Mol Med 27(13):1775–1789. https://doi.org/10.1111/jcmm.17784 - DOI - PubMed - PMC
1. Xu B, Fan F, Liu Y, Liu Y, Zhou L, Yu H (2023) Distinct effects of familial Parkinson’s disease-associated mutations on α-synuclein phase separation and amyloid aggregation. Biomolecules 13(5):726 - PubMed - PMC - DOI

Publication types

Actions

LinkOut - more resources

Full Text Sources
- Springer

[1] Al-kuraishy HM, Al-Gareeb AI, Kaushik A, Kujawska M, Ahmed EA, Batiha GES (2023) SARS-COV-2 infection and Parkinson’s disease: possible links and perspectives. J Neurosci Res 101(6):952–975 - PubMed - DOI

[2] Al-kuraishy HM, Al-Gareeb AI, Kaushik A, Kujawska M, Ahmed EA, Batiha GES (2023) SARS-COV-2 infection and Parkinson’s disease: possible links and perspectives. J Neurosci Res 101(6):952–975 - PubMed - DOI

[3] Al-Kuraishy HM, Jabir MS, Al-Gareeb AI, Albuhadily AK (2023) The conceivable role of prolactin hormone in Parkinson disease: the same goal but with different ways. Ageing Res Rev 91:102075. https://doi.org/10.1016/j.arr.2023.102075 - DOI - PubMed

[4] Al-Kuraishy HM, Jabir MS, Al-Gareeb AI, Albuhadily AK (2023) The conceivable role of prolactin hormone in Parkinson disease: the same goal but with different ways. Ageing Res Rev 91:102075. https://doi.org/10.1016/j.arr.2023.102075 - DOI - PubMed

[5] Heras-Garvin A, Stefanova N (2020) From synaptic protein to prion: the long and controversial journey of α-synuclein. Front Synaptic Neurosci 12:584536 - PubMed - PMC - DOI

[6] Heras-Garvin A, Stefanova N (2020) From synaptic protein to prion: the long and controversial journey of α-synuclein. Front Synaptic Neurosci 12:584536 - PubMed - PMC - DOI

[7] Alrouji M, Al-kuraishy HM, Al-Gareeb AI, Alexiou A, Papadakis M, Jabir MS et al (2023) NF-κB/NLRP3 inflammasome axis and risk of Parkinson’s disease in type 2 diabetes mellitus: a narrative review and new perspective. J Cell Mol Med 27(13):1775–1789. https://doi.org/10.1111/jcmm.17784 - DOI - PubMed - PMC

[8] Alrouji M, Al-kuraishy HM, Al-Gareeb AI, Alexiou A, Papadakis M, Jabir MS et al (2023) NF-κB/NLRP3 inflammasome axis and risk of Parkinson’s disease in type 2 diabetes mellitus: a narrative review and new perspective. J Cell Mol Med 27(13):1775–1789. https://doi.org/10.1111/jcmm.17784 - DOI - PubMed - PMC

[9] Xu B, Fan F, Liu Y, Liu Y, Zhou L, Yu H (2023) Distinct effects of familial Parkinson’s disease-associated mutations on α-synuclein phase separation and amyloid aggregation. Biomolecules 13(5):726 - PubMed - PMC - DOI

[10] Xu B, Fan F, Liu Y, Liu Y, Zhou L, Yu H (2023) Distinct effects of familial Parkinson’s disease-associated mutations on α-synuclein phase separation and amyloid aggregation. Biomolecules 13(5):726 - PubMed - PMC - DOI

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Similar articles

References

Publication types

LinkOut - more resources

Full Text Sources

Abstract

Similar articles

References

Publication types

Related information

LinkOut - more resources

Full Text Sources