Brain HealthMetabolic Reprogramming Offers New Path to Halt Progressive Multiple Sclerosis
Multiple sclerosis has long been treated as a pure autoimmune disease, but modern immunotherapies fail to stop progressive neurodegeneration. This review reframes MS as also a metabolic disorder: proinflammatory immune cells rely on aerobic glycolysis driven by mTOR and HIF-1α, while protective cells and neurons depend on fatty acid oxidation via AMPK. When glycolysis dominates, chronic inflammation persists and myelin repair fails. Excitingly, existing MS drugs like dimethyl fumarate and teriflunomide appear to work partly through metabolic mechanisms. Emerging therapies — including metformin (AMPK activation), glutaminase inhibitors, mTOR inhibitors, and NAD+ precursors — specifically target this metabolic imbalance to promote remyelination and reduce neuroinflammation. The authors argue this metabolic lens opens a new therapeutic era for progressive MS.
