GSK-3?-mediated regulation of Nrf2/HO-1 signaling as a new therapeutic approach in the treatment of movement disorders

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dc.contributor.authorSoni, Divya
dc.contributor.authorKumar, Puneet
dc.date.accessioned2024-01-21T10:55:04Z
dc.date.accessioned2024-08-14T07:44:20Z
dc.date.available2024-01-21T10:55:04Z
dc.date.available2024-08-14T07:44:20Z
dc.date.issued2022-07-27T00:00:00
dc.description.abstractMovement disorders are neurological conditions characterized by involuntary motor movements, such as dystonia, ataxia, chorea myoclonus, tremors, Huntington�s disease (HD), and Parkinson�s disease (PD). It is classified into two categories: hypokinetic and hyperkinetic movements. Globally, movement disorders are a major cause of death. The pathophysiological process is initiated by excessive ROS generation, mitochondrial dysfunction, neuroinflammation, and neurotransmitters imbalance that lead to motor dysfunction in PD and HD patients. Several endogenous targets including Nrf2 maintain oxidative balance in the body. Activation of Nrf2 signaling is regulated by the enzyme glycogen synthase kinase (GSK-3?). In the cytoplasm, inhibition of GSK-3? regulates cellular proliferation, homeostasis, and apoptotic process by stimulating the nuclear factor erythroid 2 (Nrf2) pathway which is involved in the elevation of the cellular antioxidant enzymes which controls the ROS generation. The activation of Nrf2 increases the expression of antioxidant response elements (ARE), such as (Hemeoxygenase-1) HO-1, which decreases excessive cellular stress, mitochondrial dysfunction, apoptosis, and neuronal degeneration, which is the major cause of motor dysfunction. The present review explores the GSK-3?-mediated neuroprotection in various movement disorders through the Nrf2/HO-1 antioxidant pathway. This review provides a�link between GSK-3? and the Nrf2/HO-1 signaling pathway in the treatment of PD and HD. In addition to that it highlights various GSK-3? inhibitors and the Nrf2/HO-1 activators, which exert robust neuroprotection against motor disorders. Therefore, the present review will help in the discovery of new therapy for PD and HD patients. � 2022, The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.en_US
dc.identifier.doi10.1007/s43440-022-00390-z
dc.identifier.issn22995684
dc.identifier.urihttp://10.2.3.109/handle/32116/4328
dc.identifier.urlhttps://link.springer.com/10.1007/s43440-022-00390-z
dc.language.isoen_USen_US
dc.publisherSpringer Science and Business Media Deutschland GmbHen_US
dc.subjectGSK-3?en_US
dc.subjectHuntington�s diseaseen_US
dc.subjectMovement disordersen_US
dc.subjectNeuroprotectionen_US
dc.subjectNrf2/HO-1en_US
dc.subjectParkinson�s diseaseen_US
dc.titleGSK-3?-mediated regulation of Nrf2/HO-1 signaling as a new therapeutic approach in the treatment of movement disordersen_US
dc.title.journalPharmacological Reportsen_US
dc.typeReviewen_US
dc.type.accesstypeClosed Accessen_US

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