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GSK-3β-mediated regulation of Nrf2/HO-1 signaling as a new therapeutic approach in the treatment of movement disorders.
Pharmacol Rep. 2022 Aug; 74(4):557-569.PR

Abstract

Movement 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-3β). In the cytoplasm, inhibition of GSK-3β 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-3β-mediated neuroprotection in various movement disorders through the Nrf2/HO-1 antioxidant pathway. This review provides a link between GSK-3β and the Nrf2/HO-1 signaling pathway in the treatment of PD and HD. In addition to that it highlights various GSK-3β 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.

Authors+Show Affiliations

Department of Pharmacology, Central University of Punjab, Ghudda, Bathinda, India.Department of Pharmacology, Central University of Punjab, Ghudda, Bathinda, India. puneet.bansal@cup.edu.in.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

35882765

Citation

Soni, Divya, and Puneet Kumar. "GSK-3β-mediated Regulation of Nrf2/HO-1 Signaling as a New Therapeutic Approach in the Treatment of Movement Disorders." Pharmacological Reports : PR, vol. 74, no. 4, 2022, pp. 557-569.
Soni D, Kumar P. GSK-3β-mediated regulation of Nrf2/HO-1 signaling as a new therapeutic approach in the treatment of movement disorders. Pharmacol Rep. 2022;74(4):557-569.
Soni, D., & Kumar, P. (2022). GSK-3β-mediated regulation of Nrf2/HO-1 signaling as a new therapeutic approach in the treatment of movement disorders. Pharmacological Reports : PR, 74(4), 557-569. https://doi.org/10.1007/s43440-022-00390-z
Soni D, Kumar P. GSK-3β-mediated Regulation of Nrf2/HO-1 Signaling as a New Therapeutic Approach in the Treatment of Movement Disorders. Pharmacol Rep. 2022;74(4):557-569. PubMed PMID: 35882765.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GSK-3β-mediated regulation of Nrf2/HO-1 signaling as a new therapeutic approach in the treatment of movement disorders. AU - Soni,Divya, AU - Kumar,Puneet, Y1 - 2022/07/26/ PY - 2022/05/11/received PY - 2022/07/12/accepted PY - 2022/07/09/revised PY - 2022/7/27/pubmed PY - 2022/8/6/medline PY - 2022/7/26/entrez KW - GSK-3β KW - Huntington’s disease KW - Movement disorders KW - Neuroprotection KW - Nrf2/HO-1 KW - Parkinson’s disease SP - 557 EP - 569 JF - Pharmacological reports : PR JO - Pharmacol Rep VL - 74 IS - 4 N2 - Movement 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-3β). In the cytoplasm, inhibition of GSK-3β 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-3β-mediated neuroprotection in various movement disorders through the Nrf2/HO-1 antioxidant pathway. This review provides a link between GSK-3β and the Nrf2/HO-1 signaling pathway in the treatment of PD and HD. In addition to that it highlights various GSK-3β 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. SN - 1734-1140 UR - https://www.unboundmedicine.com/medline/citation/35882765/GSK_3β_mediated_regulation_of_Nrf2/HO_1_signaling_as_a_new_therapeutic_approach_in_the_treatment_of_movement_disorders_ L2 - https://medlineplus.gov/movementdisorders.html DB - PRIME DP - Unbound Medicine ER -