RNA m6A demethylase FTO in central nervous system disorders: Mechanisms and therapeutic implications

26/09/2026

AI Summary

FTO is an m6A RNA demethylase broadly expressed, with relatively high brain levels, linking an obesity-related protein to neural RNA regulation.
FTO modulates neural differentiation, synaptic plasticity and neuroinflammation via dynamic regulation of RNA m6A methylation, affecting neuronal function.
Altered FTO activity contributes to pathogenesis and therapeutic responses in Parkinson's, Alzheimer's, stroke, epilepsy, depression, autism and substance use disorders.

TL;DR (AI Generated)

However, accumulating evidence has subsequently identified FTO as an N6-methyladenosine (m6A) demethylase, suggesting that it may participate in various neurological processes, including neural differentiation, synaptic plasticity, and neuroinflammation, through modulation of RNA m6A methylation.

Increasing studies have demonstrated that FTO is involved in the pathophysiological mechanisms and therapeutic responses of a range of central nervous system (CNS) disorders, including Parkinson's disease, epilepsy, Alzheimer's disease, stroke, brain tumors, depression, autism, and substance use disorders.

This review summarizes the potential roles of FTO in the pathogenesis and treatment of CNS disorders, with the aim of providing novel perspectives and potential therapeutic targets for further research and clinical intervention in CNS diseases.

Basic summary

Prog Neuropsychopharmacol Biol Psychiatry. 2026 Sep 25:111942. doi: 10.1016/j.pnpbp.2026.111942. Online ahead of print.

ABSTRACT

The fat mass and obesity-associated protein (FTO) is an obesity-related protein that is widely expressed in different tissues throughout the human body, with relatively high expression levels observed in the brain. Initial investigations into FTO mainly concentrated on its involvement in the development of obesity and diabetes. However, accumulating evidence has subsequently identified FTO as an N6-methyladenosine (m6A) demethylase, suggesting that it may participate in various neurological processes, including neural differentiation, synaptic plasticity, and neuroinflammation, through modulation of RNA m6A methylation. Increasing studies have demonstrated that FTO is involved in the pathophysiological mechanisms and therapeutic responses of a range of central nervous system (CNS) disorders, including Parkinson’s disease, epilepsy, Alzheimer’s disease, stroke, brain tumors, depression, autism, and substance use disorders. This review summarizes the potential roles of FTO in the pathogenesis and treatment of CNS disorders, with the aim of providing novel perspectives and potential therapeutic targets for further research and clinical intervention in CNS diseases.

PMID:42790767 | DOI:10.1016/j.pnpbp.2026.111942

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