LINGO1 Human
Description
Introduction to LINGO1 Human
LINGO1 (Leucine-rich repeat and immunoglobulin-like domain-containing protein 1) is a transmembrane glycoprotein encoded by the LINGO1 gene located on human chromosome 15q24. It is a critical component of the central nervous system (CNS), primarily expressed in neurons and oligodendrocytes, with negligible presence in non-neural tissues . LINGO1 regulates axon regeneration, myelination, and neuronal survival through interactions with the Nogo-66 receptor (NgR1) and downstream signaling pathways .
Domain Organization
Negative Regulation of Myelination
LINGO1 inhibits oligodendrocyte differentiation and myelination via RhoA-GTP activation, blocking maturation even in the absence of NgR1 or p75 .
Axon Regeneration Inhibition
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Forms a ternary complex with NgR1 and p75/TROY, activating RhoA/ROCK pathways to suppress neurite outgrowth after CNS injury .
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Soluble LINGO1-Fc antagonists improve functional recovery in spinal cord injury models .
Genetic Variants and Disease Risk
Mechanistic Insights
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BK Channel Regulation: LINGO1 binds BK channels, inducing rapid inactivation and reducing membrane expression, which may drive tremor phenotypes .
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EGFR-PI3K-Akt Pathway: LINGO1 inhibits EGFR signaling, impairing Purkinje cell survival and contributing to cerebellar degeneration .
Antagonist Development
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BIIB033 (Opicinumab): Anti-LINGO1 monoclonal antibody promotes remyelination in Phase II trials for multiple sclerosis .
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Small-Molecule Inhibitors: Block LINGO1-NgR1 interactions, showing efficacy in preclinical spinal cord injury models .
Experimental Outcomes
| Therapy | Effect | Stage |
|---|---|---|
| BIIB033 | Improved visual evoked potentials in MS patients | Phase II |
| LINGO1-Fc Fusion Protein | Enhanced axon regeneration in rodent SCI models | Preclinical |
Expression and Isoforms
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Tissue Specificity: Predominantly expressed in CNS (hippocampus, thalamus, cerebral cortex) .
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Isoforms: Over 12 splice variants identified, differing in 5′ untranslated regions but sharing the conserved coding sequence .
Future Research Directions
Product Specs
Q&A
FAQs for LINGO-1 (Human) Research
Curated for academic researchers with emphasis on experimental design and data interpretation
Advanced Research Questions
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How to resolve discrepancies in LINGO-1 signaling outcomes across neural cell types?
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What strategies optimize monoclonal antibody development against LINGO-1’s functional epitopes?
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Epitope mapping: Use hydrogen-deuterium exchange mass spectrometry (HDX-MS) to identify solvent-accessible regions in the LRR/Ig-like domains .
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Humanization protocol:
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Clone murine anti-LINGO-1 Fab fragments into phage display libraries .
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Select variants with <1 nM affinity via surface plasmon resonance (SPR) .
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Validate neutralization efficacy in SH-SY5Y neurite outgrowth assays .
Critical data gap: No crystal structures of antibody-LINGO-1 complexes are publicly available .
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Methodological Challenges
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How to address confounding variables in LINGO-1 biomarker studies for demyelinating diseases?
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Preanalytical factors: Standardize CSF collection protocols (time-to-processing <2 hrs) to prevent LINGO-1 degradation .
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Assay interference: Use EDTA-free buffers and validate ELISA with spike-recovery experiments (target recovery: 85-115%) .
Contradictory finding: Elevated LINGO-1 in MS CSF vs. reduced levels in ALS – may reflect disease-specific regulation .
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What computational tools predict LINGO-1 interactome dynamics?
Data Reproducibility Checklist
Product Science Overview
The LRIT1 gene encodes a protein that contains leucine-rich repeats (LRRs) and immunoglobulin (Ig)-like domains. These structural motifs are crucial for protein-protein interactions and are commonly found in proteins involved in cell adhesion, signaling, and immune responses . The LRRs are typically involved in forming a horseshoe-shaped structure that facilitates interactions with other proteins, while the Ig-like domains contribute to the protein’s stability and binding capabilities .
Human recombinant LRIT1 is used in various research applications to study its function and role in disease. Recombinant proteins are produced through genetic engineering techniques, allowing scientists to investigate the protein’s properties and interactions in a controlled environment. This research is crucial for developing targeted therapies and understanding the molecular mechanisms underlying diseases associated with LRIT1 .
