LINGO-1 (LRR and Ig domain-containing, nogo receptor interacting protein) is a protein highly expressed in the brain but not in other tissues. There are currently two other known human paralogs- LINGO-2 and LINGO-3. LINGO-1 contains 12 leucine-rich repeat (LRR) motifs flanked by N- and C- terminal capping domains, one immunoglobulin (Ig) domain, a transmembrane domain and a short cytoplasmic tail. The cytoplasmic tail contains a canonical epidermal growth factor receptor-like tyrosine phosphorylation site. LINGO-1 is highly conserved evolutionary with human and mouse orthologues, sharing 99.5% identity. LINGO-1 binds both to Nogo-66 receptor (NgR1) and to p75 neurotrophin receptor simultaneously and can form a ternary complex¹.

In animal models, LINGO-1 expression is upregulated in rat spinal cord injury, experimental autoimmune encephalomyelitis, neurotoxic lesions and glaucoma. In humans, LINGO-1 expression is increased in oligodendrocyte progenitor cells from demyelinated white matter of multiple sclerosis post-mortem samples, and in dopaminergic neurons from Parkinson’s disease brains. LINGO-1 negatively regulates oligodendrocyte differentiation and myelination, neuronal survival and axonal regeneration by activating the RhoA and inhibiting protein kinase B (Akt) phosphorylation signaling pathways².