Axon remyelination

Axon remyelination is a complex biological process in the central nervous system (CNS) where new myelin sheaths are generated around demyelinated axons. This process is primarily executed by oligodendrocyte precursor cells (OPCs) that respond to injury by migrating to the site of damage, proliferating, and differentiating into mature oligodendrocytes [Nature Reviews Neurology, 2018, 14(10):613–625]. While remyelination occurs spontaneously in the early stages of diseases like Multiple Sclerosis, it often fails in chronic lesions, leading to permanent axonal loss and progressive neurological disability [PubMed: 28993036]. From a therapeutic perspective, axon remyelination is not a single molecular target but a physiological goal achieved by modulating various receptors and pathways, such as the muscarinic M1 receptor (targeted by Clemastine) or the LINGO-1 protein (targeted by Opicinumab) [Lancet, 2017, 390:2482-2491; Lancet Neurology, 2019, 18:845-856]. Successful remyelination restores saltatory conduction, which speeds up nerve impulse transmission, and provides essential metabolic and trophic support to the underlying axon, thereby preventing neurodegeneration. Current research focuses on identifying small molecules and biologics that can overcome the inhibitory environment of the glial scar to trigger this regenerative response in patients with demyelinating disorders [J. Neurosci, 2011, 31:14967-14973].

Other names

Myelin repairCNS remyelinationSpontaneous remyelinationOligodendrocyte precursor cell differentiation

Therapeutic strategies for axon remyelination focus on promoting the recruitment, proliferation, and differentiation of oligodendrocyte precursor cells (OPCs) into mature, myelinating oligodendrocytes, or by neutralizing inhibitory molecules in the lesion microenvironment (e.g., LINGO-1) [Nature Reviews Neurology, 2018, 14(10):613–625].