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The Role of Δfosb in the Pathogenesis of Levodopa-Induced Dyskinesia: Mechanisms and Therapeutic Strategies Publisher



Zamanian MY1, 2 ; Kamran Z3 ; Tavakoli MR4 ; Oghenemaro EF5 ; Abohassan M6 ; Kubaev A7 ; Nathiya D8 ; Kaur P9 ; Zwamel AH10, 11, 12 ; Abdulamer RS13
Authors
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Authors Affiliations
  1. 1. Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
  2. 2. Department of Physiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, 6718773654, Iran
  3. 3. Department of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  4. 4. Pharmaceutical Sciences and Cosmetic Products Research Center, Kerman University of Medical Sciences, Kerman, Iran
  5. 5. Department of Pharmaceutical Microbiology & Biotechnology, Faculty of Pharmacy, Delta State University, Abraka, United States
  6. 6. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
  7. 7. Department of Maxillofacial Surgery, Samarkand State Medical University, 18 Amir Temur Street, Samarkand, 140100, Uzbekistan
  8. 8. Department of Pharmacy Practice, NIMS Institute of Pharmacy, NIMS University Rajasthan, Jaipur, India
  9. 9. Chandigarh Pharmacy College, Chandigarh Group of Colleges-Jhanjeri, Punjab, Mohali, 140307, India
  10. 10. Medical Laboratory Technique College, The Islamic University, Najaf, Iraq
  11. 11. Medical Laboratory Technique College, The Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq
  12. 12. Medical Laboratory Technique College, The Islamic University of Babylon, Babylon, Iraq
  13. 13. Department of Medical Laboratories Technology, Al-Nisour University College, Nisour Seq. Karkh, Baghdad, Iraq

Source: Molecular Neurobiology Published:2025


Abstract

Levodopa-induced dyskinesia (LID) represents a significant complication associated with the long-term administration of levodopa (L-DOPA) for the treatment of Parkinson’s disease (PD). This review examines the critical role of ΔFosB, a transcription factor, in the pathogenesis of LID and explores potential therapeutic interventions. ΔFosB accumulates within the striatum in response to chronic dopaminergic stimulation, thereby driving maladaptive changes that culminate in dyskinesia. Its persistent expression modifies gene transcription, influencing neuronal plasticity and contributing to the sustained presence of dyskinetic movements. This study explains how ΔFosB functions at the molecular level, focusing on its connections with dopamine D1 receptors, the cAMP/PKA signaling pathway, and its regulatory effects on downstream targets such as DARPP-32 and GluA1 AMPA receptor subunits. Additionally, it examines how neuronal nitric oxide synthase (nNOS) affects ΔFosB levels and the development of LID. This review also considers the interactions between ΔFosB and other signaling pathways, such as ERK and mTOR, in the context of LID and striatal plasticity. Emerging therapeutic strategies targeting ΔFosB and its associated pathways include pharmacological interventions like ranitidine, 5-hydroxytryptophan, and carnosic acid. Furthermore, this study addresses the role of JunD, another component of the AP-1 transcription factor complex, in the pathogenesis of LID. Understanding the molecular mechanisms by which ΔFosB contributes to LID offers promising avenues for developing novel treatments that could mitigate dyskinesia and improve the quality of life for PD patients undergoing long-term L-DOPA therapy. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.
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