Redox therapy for neuropsychiatric disorders: Molecular mechanisms and biomarker development

Redox dysregulation, characterized by an imbalance in the NAD⁺ [nicotinamide adenine dinucleotide (oxidized form)]/NADH (reduced form of NAD⁺) ratio, is implicated in neurodegenerative and psychiatric disorders such as Alzheimer's disease and schizophrenia. This imbalance contributes to mitochondrial dysregulation, oxidative stress, and inflammation. Despite promising preclinical studies supporting therapeutic strategies aimed at restoring redox balance and thereby rescuing brain bioenergetic deficits, clinical outcomes and efficacy remain limited. Progress has been hindered by the incomplete understanding of NAD⁺ subcellular cycling, as well as a lack of in vivo biomarkers measuring target engagement of redox status and mitochondrial function. Thus, this review examines molecular mechanisms of NAD (nicotinamide adenine dinucleotide)-related bioenergetic deficits, current and emerging NAD-targeted therapies, and recent advances in the development of neuroimaging biomarkers, emphasizing personalized and mechanism-driven approaches.