Sep 2026· Proceedings of the National Academy of Sciences of the United States of America· Vol 123· 0 citations· 126 references
Medicine
TL;DR
It is demonstrated that loss of membrane-bound catechol-O-methyltransferase (MB-COMT), a key degrader of DA in the brain, disrupts cellular metal handling and redox-regulatory pathways and triggers widespread protein misfolding in schizophrenia and Parkinson’s disease.
Abstract
Significance Dysregulated dopamine (DA) signaling and impaired redox homeostasis are central to the pathophysiology of schizophrenia (SCZ) and Parkinson’s disease (PD). Here, Tripathi and Chakraborty et al. demonstrate that loss of membrane-bound catechol-O-methyltransferase (MB-COMT), a key degrader of DA in the brain, disrupts cellular metal handling and redox-regulatory pathways and triggers widespread protein misfolding. Such disturbances are observed across both disorders, underscoring a critical role of MB-COMT in DA homeostasis in preventing neuropathology and identifying related pathways as potential therapeutic targets.
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