Leucine-rich repeat and immunoglobulin-like domain-containing protein 1 (LINGO1) (LINGO1)

Leucine-rich repeat and immunoglobulin-like domain-containing protein 1 (LINGO1) is a transmembrane protein primarily expressed in the central nervous system (CNS) that serves as a potent negative regulator of axonal regeneration and oligodendrocyte differentiation [UniProt: Q96FE5]. It functions as a key component of the Nogo-66 receptor 1 (NgR1) signaling complex, which also includes p75 or TROY, to activate the RhoA pathway and inhibit the maturation of oligodendrocyte precursor cells (OPCs) into myelin-producing cells [PubMed: 15475957]. In neurodegenerative conditions such as Multiple Sclerosis (MS) and Parkinson's disease, LINGO1 expression is often elevated, contributing to the failure of endogenous repair mechanisms [PubMed: 16244655]. Therapeutic interventions, most notably the monoclonal antibody opicinumab (BIIB033), have been developed to block LINGO1 function in hopes of promoting remyelination and neuroprotection, although clinical trials have faced challenges in demonstrating significant efficacy [ClinicalTrials.gov: NCT01864148]. While the protein is the primary target of clinical-stage drugs, the LINGO1 mRNA transcript is a target for experimental RNA interference (RNAi) and antisense oligonucleotide (ASO) strategies aimed at reducing protein levels at the source [PubMed: 21841784].

Other names

LRRN6ALERN1UNQ201FLJ14594

Inhibition of LINGO1 signaling to promote oligodendrocyte precursor cell differentiation and axonal remyelination.