Pantethine and Neurodegeneration: A Coenzyme A-Centered Framework Linking Metabolism, Neuroinflammation, and Mitochondrial Dysfunction
7 affiliations
- 1Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília 17525-902, SP, Brazil
- 2Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marília (UNIMAR), Marília 17525-902, SP, Brazil
- 3Department of Pharmacology, College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
- 4Systematic Reviews and Meta-Analyses Center, School of Philosophy and Sciences, São Paulo State University, Marília 17525-900, SP, Brazil
- 5Department of Neurology, Albert Szent-Györgyi Medical School, University of Szeged, H-6725 Szeged, Hungary
- 6HUN-REN-SZTE Neuroscience Research Group, Danube Neuroscience Research Laboratory, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), H-6725 Szeged, Hungary
- 7Research Coordination, UNIMAR Charity Hospital, School of Medicine, University of Marília (UNIMAR), Marília 17525-902, SP, Brazil
Abstract
Neurodegenerative diseases are a growing global health burden associated with aging and characterized by progressive neuronal dysfunction, metabolic failure, mitochondrial impairment, oxidative stress, and chronic neuroinflammation. Among the metabolic pathways implicated in these disorders, coenzyme A (CoA)-linked biology has emerged as a potentially important but still underexplored contributor to neuronal resilience and vulnerability. Pantethine, a disulfide derivative of pantetheine and a CoA-related metabolic precursor, has attracted attention because of its reported effects on cellular metabolism, redox balance, and inflammatory signaling. However, its relevance across neurodegenerative diseases remains unevenly defined, with direct support strongest in pantothenate kinase-associated neurodegeneration (PKAN) and more limited evidence in common disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). This narrative review critically examines the mechanistic and translational evidence linking pantethine to neurodegeneration. PKAN represents the most logical disease context for pantethine investigation because impaired CoA biosynthesis is proximal to disease pathogenesis, although pantethine remains investigational and its clinical efficacy has not been established. By contrast, proposed applications in AD and PD remain highly theoretical and hypothesis-generating. Nevertheless, research on pantethine and related CoA-restoring strategies may identify new intervention targets across neurodegenerative diseases and other disorders characterized by impaired cellular bioenergetics, including selected neuropsychiatric disorders. These possibilities require biomarker-informed, disease-specific studies that establish active-species exposure, target engagement, and clinically meaningful effects.
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BibTeX
@article{simili2026pantethine,
title = {{Pantethine and Neurodegeneration: A Coenzyme A-Centered Framework Linking Metabolism, Neuroinflammation, and Mitochondrial Dysfunction}},
author = {Otávio Augusto Garcia Simili and Gabriel Magno de Carvalho and Raissa Santana Dias Simões and Claudia Rucco Penteado Detregiachi and Eliana de Souza Bastos Mazuqueli Pereira and Virgínia Maria Cavallari Strozze Catharin and Giovani Augusto da Silva and Vitor B. Miola and Anupam Bishayee and Vitor E. Valenti and László Vécsei and Masaru Tanaka and Sandra Maria Barbalho},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219926},
url = {https://www.mdpi.com/1422-0067/27/21/9926},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pantethine and Neurodegeneration: A Coenzyme A-Centered Framework Linking Metabolism, Neuroinflammation, and Mitochondrial Dysfunction
AU - Otávio Augusto Garcia Simili
AU - Gabriel Magno de Carvalho
AU - Raissa Santana Dias Simões
AU - Claudia Rucco Penteado Detregiachi
AU - Eliana de Souza Bastos Mazuqueli Pereira
AU - Virgínia Maria Cavallari Strozze Catharin
AU - Giovani Augusto da Silva
AU - Vitor B. Miola
AU - Anupam Bishayee
AU - Vitor E. Valenti
AU - László Vécsei
AU - Masaru Tanaka
AU - Sandra Maria Barbalho
PY - 2026
DA - 2026/11/05
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219926
UR - https://www.mdpi.com/1422-0067/27/21/9926
AB - Neurodegenerative diseases are a growing global health burden associated with aging and characterized by progressive neuronal dysfunction, metabolic failure, mitochondrial impairment, oxidative stress, and chronic neuroinflammation. Among the metabolic pathways implicated in these disorders, coenzyme A (CoA)-linked biology has emerged as a potentially important but still underexplored contributor to neuronal resilience and vulnerability. Pantethine, a disulfide derivative of pantetheine and a CoA-related metabolic precursor, has attracted attention because of its reported effects on cellular metabolism, redox balance, and inflammatory signaling. However, its relevance across neurodegenerative diseases remains unevenly defined, with direct support strongest in pantothenate kinase-associated neurodegeneration (PKAN) and more limited evidence in common disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). This narrative review critically examines the mechanistic and translational evidence linking pantethine to neurodegeneration. PKAN represents the most logical disease context for pantethine investigation because impaired CoA biosynthesis is proximal to disease pathogenesis, although pantethine remains investigational and its clinical efficacy has not been established. By contrast, proposed applications in AD and PD remain highly theoretical and hypothesis-generating. Nevertheless, research on pantethine and related CoA-restoring strategies may identify new intervention targets across neurodegenerative diseases and other disorders characterized by impaired cellular bioenergetics, including selected neuropsychiatric disorders. These possibilities require biomarker-informed, disease-specific studies that establish active-species exposure, target engagement, and clinically meaningful effects.
SN - 1422-0067
ER -