Pantethine and Neurodegeneration: A Coenzyme A-Centered Framework Linking Metabolism, Neuroinflammation, and Mitochondrial Dysfunction

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.