LINGO1

LINGO1 (Leucine-rich repeat and immunoglobulin domain-containing protein 1), also termed LRRIG1, functions as a negative regulatory component in the central nervous system. It modulates neuronal survival and axonal regeneration by antagonizing TrkB receptor signaling, thereby suppressing neurotrophin-mediated neural repair. Structurally, LINGO1 interacts with Nogo-66, NgR1, and p75NTR to form a receptor complex that activates RhoA/ROCK signaling, a pathway critical for cytoskeletal dynamics and myelination inhibition. Its overexpression disrupts oligodendrocyte differentiation and remyelination processes, contributing to neurodegenerative pathologies.
Dysregulation of LINGO1 is implicated in multiple sclerosis, Parkinson’s disease, and essential tremor. Preclinical studies highlight its therapeutic potential, with monoclonal antibodies like Antogin-3 demonstrating efficacy in promoting remyelination and neuroprotection in MS models. Small-molecule inhibitors targeting LINGO1’s extracellular domain and gene-silencing approaches using antisense oligonucleotides are under investigation. Recent phase I trials of anti-LINGO1 biologics showed favorable safety profiles, though efficacy in human demyelinating disorders remains to be validated in advanced clinical stages.