Exercise, Demethylase FTO, Neurological Disorders, and Neuropathic Pain: Potential Molecular Mechanisms

This review aims to summarize the role of fat mass and obesity-associated protein (FTO) in neurological disorders and neuropathic pain (NP).

Key findings suggest that in neurological disorders such as Alzheimer's disease, Parkinson's disease, and depression, FTO-regulated m⁶A modification plays a critical role in the hippocampus and striatum. FTO-mediated m⁶A modification is involved in the pathological processes of NP. These findings suggest that FTO may serve as a potential therapeutic target for neurological disorders and NP. Common mechanisms may include the regulation of downstream mTOR and BDNF/TrkB signaling pathways, as well as modulation of neuronal excitability and synaptic plasticity. However, research on the relationship between exercise and m⁶A modification remains in its early stages. Emerging evidence suggests that exercise reduces FTO expression and increases m⁶A levels in the hippocampus and hypothalamus, indicating that exercise may serve as an effective intervention for modulating epigenetic modifications in the central nervous system.

This implies that exercise may serve as an effective intervention for modulating epigenetic modifications, potentially by downregulating the demethylase FTO, regulating m⁶A modification, enhancing synaptic plasticity, modulating neuronal excitability, and providing neuroprotection, thereby contributing to disease mitigation. We hypothesize that exercise may regulate neurological disorders and NP through FTO-mediated m⁶A modification, with FTO potentially serving as a biomarker.