THE SCIENTIFIC DISCUSSION OF KEY ISSUE ASPECTS OF MITOCHONDRIAL DYSFUNCTION AND PHARMACOTHERAPEUTIC MANAGEMENT STRATEGIES IN PARKINSON'S DISEASE: FOCUS ON MITOPHAGY AND NAD+ METABOLISM

Nodar Sulashvili; Elene Abzianidze; Margarita Beglaryan; Luiza Gabunia; Nana Gorgaslidze; Nato Alavidze; Tharaka Srinatha Dunuwila; Kshitij Kumar; Jugal Kishore; Ketevan Ghambashidze; Marika Sulashvili; Lela Grigolia; Kakhaber Robakidze; Irine Zarnadze; Shalva (Davit) Zarnadze; David Aphkhazava

doi:10.52340/gs.2025.07.03.25

Authors

Nodar Sulashvili Tbilisi State Medical University , Georgia https://orcid.org/0000-0002-9005-8577
Elene Abzianidze Tbilisi State Medical University , Georgia
Margarita Beglaryan Yerevan State Medical University After Mkhitar Heratsi, Armenia https://orcid.org/0000-0003-3697-6390
Luiza Gabunia Tbilisi State Medical University , Georgia https://orcid.org/0000-0003-0856-2684
Nana Gorgaslidze Tbilisi State Medical University , Georgia https://orcid.org/0000-0002-4563-5224
Nato Alavidze Akaki Tsereteli State University , Georgia https://orcid.org/0000-0001-6695-5924
Tharaka Srinatha Dunuwila Alte University , Georgia
Kshitij Kumar St Stephen’s hospital, India
Jugal Kishore Georgian National University SEU , Georgia
Ketevan Ghambashidze Tbilisi State Medical University , Georgia https://orcid.org/0000-0002-3845-9306
Marika Sulashvili Tbilisi State Medical University , Georgia
Lela Grigolia Caucasus International University , Georgia
Kakhaber Robakidze Caucasus International University , Georgia
Irine Zarnadze Tbilisi State Medical University , Georgia
Shalva (Davit) Zarnadze Tbilisi State Medical University , Georgia
David Aphkhazava Alte University , Georgia

Vol. 7 No. 3 (2025)

ARTICLES

Published August 4, 2025

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Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons and the accumulation of α-synuclein in Lewy bodies. Mitochondrial dysfunction plays a central role in both sporadic and familial PD, contributing to bioenergetic deficits, oxidative stress, and mitochondrial DNA (mtDNA) damage. This review examines the pivotal role of mitophagy—the selective autophagy of damaged mitochondria—in maintaining mitochondrial integrity and explores therapeutic strategies aimed at restoring mitochondrial function. Additionally, we discuss the significance of Nicotinamide adenine dinucleotide (NAD+) metabolism in mitigating mitochondrial dysfunction and its implications for PD pathogenesis. Emerging pharmacological interventions targeting mitophagy and NAD+ metabolism are proposed as promising therapeutic avenues to slow or halt neurodegeneration in PD. Mitochondrial dysfunction plays a central role in the pathogenesis of Parkinson’s disease (PD), contributing to neuronal degeneration through oxidative stress, bioenergetic failure, and impaired quality control mechanisms. This review critically examines key aspects of mitochondrial dysfunction in PD, with a focus on mitophagy and NAD+ metabolism as pivotal therapeutic targets. Dysregulated mitophagy, particularly involving PINK1-Parkin signaling, leads to the accumulation of damaged mitochondria, exacerbating neurodegeneration. Additionally, declining NAD+ levels impair mitochondrial bioenergetics and cellular resilience, further aggravating PD progression. Emerging therapeutic strategies, including NAD+ supplementation, mitophagy enhancers, and metabolic modulators, hold promise for restoring mitochondrial homeostasis and neuroprotection. By integrating current research, this discussion highlights the potential of targeting mitochondrial pathways to develop novel interventions for PD, while addressing remaining challenges in translational application.

Sulashvili, N., Abzianidze, E., Beglaryan, M., Gabunia, L., Gorgaslidze, N., Alavidze, N., … Aphkhazava, D. (2025). THE SCIENTIFIC DISCUSSION OF KEY ISSUE ASPECTS OF MITOCHONDRIAL DYSFUNCTION AND PHARMACOTHERAPEUTIC MANAGEMENT STRATEGIES IN PARKINSON’S DISEASE: FOCUS ON MITOPHAGY AND NAD+ METABOLISM. Georgian Scientists, 7(3), 397–442. https://doi.org/10.52340/gs.2025.07.03.25

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Nodar Sulashvili, Tbilisi State Medical University

MD, PhD, Doctor of Pharmaceutical and Pharmacological Sciences in Medicine, Invited Lecturer (Invited Professor) of Scientific Research-Skills Center at Tbilisi State Medical University; Professor of Medical and Clinical Pharmacology of International School of Medicine at Alte University; Professor of Pharmacology of Faculty of Medicine at Georgian National University SEU; Tbilisi, Georgia; Orcid https://orcid.org/0000-0002-9005-8577; E-mail: n.sulashvili@ug.edu.ge

Elene Abzianidze, Tbilisi State Medical University

PhD, Doctor of Biological Sciences, Academician, Emeritus Professor of Tbilisi State Medical University, Department of Molecular and Medical Genetics; Tbilisi, Georgia.

Margarita Beglaryan, Yerevan State Medical University After Mkhitar Heratsi

MD, PhD, Doctor of Pharmaceutical Sciences, Academician, Professor of Yerevan State Medical University After Mkhitar Heratsi, Head of the Department of Pharmaceutical Management, President of Association PHESA (Pharmacy and Pharmacology Education and Science Association), Yerevan, Armenia; https://orcid.org/0000-0003-3697-6390

Luiza Gabunia, Tbilisi State Medical University

MD, PhD, Doctor of Medical Sciences, Professor, Director of the Scientific Research-Skills Center at Tbilisi State Medical University, Professor, Head of the Department of Medical and Clinical Pharmacology at Tbilisi State Medical University, Clinical Pharmacologist of The First University Clinic of TSMU, Tbilisi, Georgia https://orcid.org/0000-0003-0856-2684

Nana Gorgaslidze, Tbilisi State Medical University

MD, PhD, Doctor of Pharmaceutical Sciences, Academician, Professor of Tbilisi State Medical University, Head of The Department of Social and Clinical Pharmacy, Tbilisi, Georgia. https://orcid.org/0000-0002-4563-5224

Nato Alavidze, Akaki Tsereteli State University

MD, PhD, Doctor of Pharmaceutical Sciences, Professor of Akaki Tsereteli State University, Faculty of Medicine, Department of Pharmacy, Kutaisi, Georgia. Professor, Dean Faculty of Medicine at East European University, Tbilisi, Georgia. https://orcid.org/0000-0001-6695-5924

Tharaka Srinatha Dunuwila, Alte University

MD, PhD, Associate Professor of International School of Medicine at Alte University; Tbilisi, Georgia

Kshitij Kumar, St Stephen’s hospital

MD, PGCDM, Diploma (Clinical Nephrology) Department of Nephrology (St Stephen’s hospital) Delhi; New Delhi India

Jugal Kishore, Georgian National University SEU

Laboratory of Brain Ultrastructure and Nanoarchitecture, Ivane Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia; MD student of Department of Medicine, Georgian National University SEU, Tbilisi, Georgia.

Ketevan Ghambashidze, Tbilisi State Medical University

MD, PhD, Doctor of Medical Sciences, Invited Professor of the Scientific Research Skills Center of Tbilisi State Medical University, Professor of Pathophysiology Department at Tbilisi State Medical University; Tbilisi, Georgia. https://orcid.org/0000-0002-3845-9306

Marika Sulashvili, Tbilisi State Medical University

MD, Doctor of Family Medicine, Invited Lecturer of Tbilisi State Medical University, Department of Molecular and Medical Genetics, Invited Professor of Biochemistry and Molecular and Medical Genetics at The University of Georgia; Tbilisi, Georgia.

Lela Grigolia, Caucasus International University

MD, PhD, Doctor of Medical Sciences, Professor of Faculty of Medicine at Caucasus International University; Tbilisi, Georgia

Kakhaber Robakidze, Caucasus International University

MD, PhD, Doctor of Medical Sciences, Academician, Professor of Faculty of Medicine at Caucasus International University; Doctor-Professor of National Health Center Named After Academician O. Gudushauri; Tbilisi, Georgia

Irine Zarnadze, Tbilisi State Medical University

MD, PhD, Doctor of Medical Sciences, Professor of Tbilisi State Medical University, Department of Public Health, Health Care Management, Policy and Economy, Tbilisi, Georgia

Shalva (Davit) Zarnadze, Tbilisi State Medical University

MD, PhD, Doctor of Medical Sciences, Academician, Professor of Tbilisi State Medical University, Dean of the Faculty of Public Health, Head of the Department of Nutrition, Aging Medicine, Environmental and Occupational Health, Tbilisi, Georgia

David Aphkhazava, Alte University

PhD, Doctor of Biological Sciences, Professor of International School of Medicine at Alte University, Tbilisi, Georgia

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SULASHVILI, NODAR, ARTASHES AZNAURYAN, ANNA TER-MARKOSYAN, NANA GORGASLIDZE, SEYRAN KOCHARYAN, IRINE ZARNADZE, BAGRAT YENOKYAN, et al. 2021. “MODERN SCIENTIFIC DISCUSSION OF SPECIFICITES OF THE ROLE, ACHIEVEMENTS, INNOVATIONS, PROFESSIONAL AND ENHANCEMENT PROSPECTS OF PHARMACISTS IN THE CONTEXT OF THE DEVELOPMENT OF HEALTH CARE SECTOR GLOBALLY”. Experimental and Clinical Medicine Georgia, no. 5-6 (October):38-41. https://journals.4science.ge/index.php/jecm/article/view/575.

Aphkhazava, David, Nodar Sulashvili, and Jaba Tkemaladze. 2025. “Stem Cell Systems and Regeneration”. Georgian Scientists 7 (1):271-319. https://doi.org/10.52340/gs.2025.07.01.26.

SULASHVILI, NODAR, NANA GORGASLIDZE, LUIZA GABUNIA, LEVAN RATIANI, SHORENA KHETSURIANI, VIRA KRAVCHENKO, IGOR SENIUK, MARINA GIORGOBIANI, NATIA KVIZHINADZE, and MARIKA SULASHVILI. 2024. “MANIFESTATION OF THE PARTICULARITIES OF SOME KEY ISSUE ASPECTS OF NEW IMMUNOTHERAPY CHALLENGES AND PERSPECTIVES BY CAR-T CELL THERAPY”. Experimental and Clinical Medicine Georgia, no. 4 (September):119-21. https://doi.org/10.52340/jecm.2024.04.32.

Sulashvili, Nodar, Sharon Fernando, Awad El-Hakeem, Luiza Gabunia, Nana Gorgaslidze, Margarita Beglaryan, Lali Patsia, Natia Kvizhinadze, and Marika Sulashvili. 2025. “CLOSED-LOOP CARDIOPULMONARY BYPASS SYSTEMS WITH REAL-TIME MONITORING AND PHARMACOTHERAPY STRATEGIES: INNOVATIONS, OUTCOMES, CLINICAL IMPACT AND FUTURE DIRECTIONS IN GENERAL”. Georgian Scientists 7 (2):381-419. https://doi.org/10.52340/gs.2025.07.02.36.

Sulashvili N, Jadhav RD, Beglaryan M, Gabunia L, Gorgaslidze N, Alavidze N, et al. THE SCIENTIFIC DISCUSSION OF KEY ISSUE ASPECTS OF IMMUNOPATHOGENESIS AND PHARMACOLOGICAL PROPERTIES AND PROFILES IN RELATION TO ADVERSE DRUG REACTIONS CHALLENGES, FOCUS ON MULTIDIMENSIONAL DRUG-INDUCED EOSINOPHILIA AND SYSTEMIC SYNDROME. GS [Internet]. 2025 Jul. 11 [cited 2025 Jul. 12];7(3):141-79. Available from: https://journals.4science.ge/index.php/GS/article/view/3919.

Sulashvili, Nodar, Nato Alavidze, Maka Buleishvili, Vira Kravchenko, Marika Sulashvili, Igor Seniuk, Tamar Okropiridze, Marina Giorgobiani, Lela Grigolia, and Kakhaber Robakidze. 2025. “THE MANIFESTATION OF KEY ISSUE FEATURES OF GLOBAL PERSPECTIVES ON INNOVATIVE TEACHING AND LEARNING APPROACH STRATEGIES IN HIGHER MEDICAL EDUCATION: ADVANCING STUDENT-CENTERED PRACTICES, TECHNOLOGY INTEGRATION AND COMPETENCY-BASED FRAMEWORKS ”. Scientific Journal „Spectri“ 10 (2). https://doi.org/10.52340/spectri.2024.10.01.11.

SULASHVILI, NODAR, NANA GORGASLIDZE, MARGARITA BEGLARYAN, LUIZA GABUNIA, NATIA KVIZHINADZE, TEA ZARKUA, MARINA GIORGOBIANI, NANA PEIKRISHVILI, and MARIKA SULASHVILI. 2024. “THE MANIFESTATION OF CHARACTERISTICS, OPPORTUNITIES AND CHALLENGES OF ELECTRONIC SYSTEMS AND DIGITAL INTELLIGENCE USING IN PHARMACEUTICAL SERVICES”. Experimental and Clinical Medicine Georgia, no. 4 (September):122-25. https://doi.org/10.52340/jecm.2024.04.33.

Sulashvili N, Davitashvili M, Gorgaslidze N, Gabunia L, Beglaryan M, Alavidze N, et al. THE SCIENTIFIC DISCUSSION OF SOME ISSUES OF FEATURES AND CHALLENGES OF USING OF CAR-T CELLS IN IMMUNOTHERAPY. GS [Internet]. 2024 Nov. 26 [cited 2025 Jul. 12];6(4):263-90. Available from: https://journals.4science.ge/index.php/GS/article/view/3214.

Sulashvili, Nodar, Udgam Yaduvanshi, Mohini Yadav, Luiza Gabunia, Ketevan Ghambashidze, Nana Gorgaslidze, Margarita Beglaryan, et al. 2025. “THE SCIENTIFIC DISCOURSE OF FEATURES OF CLINICAL USE AND PHARMACOLOGY OF VASOCONSTRICTORS AND THEIR IMPACT ON CARDIAC FUNCTION”. Junior Researchers 3 (1):28-68. https://doi.org/10.52340/jr.2025.03.01.02.

Sulashvili N, Nimangre RR. MANIFESTATION OF SOME ASPECTS OF CARDIOVASCULAR DISEASES, IMPLICATIONS, PHARMACOTHERAPEUTIC STRATEGIES, EFFECTS, IMPACTS AND POTENTIAL HAZARDS IN GENERAL. JR [Internet]. 2025 Feb. 7 [cited 2025 Jul. 12];3(1):1-27. Available from: https://journals.4science.ge/index.php/jr/article/view/3393.

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THE SCIENTIFIC DISCUSSION OF KEY ISSUE ASPECTS OF MITOCHONDRIAL DYSFUNCTION AND PHARMACOTHERAPEUTIC MANAGEMENT STRATEGIES IN PARKINSON'S DISEASE: FOCUS ON MITOPHAGY AND NAD+ METABOLISM

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Nodar Sulashvili, Tbilisi State Medical University

Elene Abzianidze, Tbilisi State Medical University

Margarita Beglaryan, Yerevan State Medical University After Mkhitar Heratsi

Luiza Gabunia, Tbilisi State Medical University

Nana Gorgaslidze, Tbilisi State Medical University

Nato Alavidze, Akaki Tsereteli State University

Tharaka Srinatha Dunuwila, Alte University

Kshitij Kumar, St Stephen’s hospital

Jugal Kishore, Georgian National University SEU

Ketevan Ghambashidze, Tbilisi State Medical University

Marika Sulashvili, Tbilisi State Medical University

Lela Grigolia, Caucasus International University

Kakhaber Robakidze, Caucasus International University

Irine Zarnadze, Tbilisi State Medical University

Shalva (Davit) Zarnadze, Tbilisi State Medical University

David Aphkhazava, Alte University

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