STMN2 Human
Description
Expression Profile
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Tissue Specificity: Highly enriched in neurons, particularly spinal motor neurons and cortical neurons .
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Subcellular Localization: Associates with microtubules in axons and growth cones .
Microtubule Dynamics
STMN2 destabilizes microtubules by sequestering tubulin heterodimers, facilitating axonal remodeling and vesicle transport. Phosphorylation by kinases like MAPK8 stabilizes microtubules during neurite outgrowth .
Axonal Maintenance and Regeneration
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Critical for axon regeneration post-injury: STMN2 knockdown in human motor neurons impairs lysosome trafficking and synaptic repair .
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Mouse models show STMN2 loss causes neuromuscular junction (NMJ) denervation and motor deficits, mimicking ALS pathology .
TDP-43 Pathology
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Mechanism: Nuclear loss of TDP-43 leads to inclusion of a cryptic exon in STMN2 pre-mRNA, producing a truncated nonfunctional transcript. This disrupts STMN2 synthesis, accelerating neurodegeneration .
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Disease Links:
Genetic Variants
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A CA repeat polymorphism in the STMN2 promoter (24 repeats) correlates with higher ALS risk and faster progression, independent of TDP-43 pathology .
Antisense Oligonucleotides (ASOs)
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Mechanism: Block cryptic exon splicing in STMN2 pre-mRNA, restoring full-length protein.
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Efficacy: Injected ASOs rescued STMN2 levels in TDP-43-deficient human neurons and mice, improving axonal regeneration .
| Therapeutic Approach | Target | Outcome | Study |
|---|---|---|---|
| ASO (QRL-201) | Cryptic exon in STMN2 | Restored NMJ innervation in mice | |
| dCasRx (CRISPR) | STMN2 pre-mRNA | Corrected splicing in human neurons |
Clinical Progress
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QRL-201: First-in-class ASO by QurAlis entered Phase 1 trials in 2025 for ALS, showing rescue of STMN2 in patient-derived models .
Preclinical Evidence
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Mouse Models: Conditional Stmn2 knockout mice develop progressive motor neuropathy with NMJ denervation, replicating ALS phenotypes .
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Human Neurons: TDP-43 depletion reduces STMN2 by 70–90%, impairing lysosome transport and synaptic function .
Transcriptomic Insights
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Cryptic Exon Detection: Truncated STMN2 mRNA serves as a biomarker for TDP-43 pathology in ALS/FTD patient tissues .
Challenges and Future Directions
Product Specs
The STMN2 protein solution is formulated in a buffer containing 50mM MES at pH 6.0, 0.1mM PMSF, 1 mM EDTA, and 10% Glycerol.
The purity of this product is greater than 85.0% as determined by SDS-PAGE analysis.
Product Science Overview
Stathmin-2 is primarily involved in the regulation of microtubule stability . When phosphorylated by MAPK8, it stabilizes microtubules and consequently controls neurite length in cortical neurons . This regulatory role is essential for neuronal growth and development . Additionally, STMN2 is thought to be involved in osteogenesis .
The protein is implicated in several biological processes, including:
- Microtubule Depolymerization: STMN2 negatively regulates microtubule polymerization and depolymerization .
- Neuronal Growth: It plays a regulatory role in neuronal growth and is involved in the development of neuron projections .
- Response to Nerve Growth Factor: STMN2 is involved in the cellular response to nerve growth factor stimulus .
Recombinant human STMN2 is produced using recombinant DNA technology, which involves inserting the human STMN2 gene into a suitable expression system to produce the protein in large quantities. This recombinant protein is used in various research applications to study its function and potential therapeutic uses.
