CNTF Rat, His
Description
Neuroprotection and Survival
rCNTF acts as a potent survival factor for neurons and glial cells:
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Motoneuron Rescue: Prevents axotomy-induced degeneration in newborn rat facial nuclei and sciatic nerves .
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Astrocyte Activation: Induces astrocyte proliferation and metabolic remodeling, reducing glutamate and neuronal metabolites (e.g., N-acetyl-aspartate) in the rat striatum .
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Retinal Protection: Promotes regeneration of cone outer segments in early-stage degeneration models .
Signaling Pathways
rCNTF activates distinct pathways depending on cell type:
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STAT3/ERK Activation: In adipocytes and preadipocytes, rCNTF induces phosphorylation of STAT3 and ERK, influencing differentiation .
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Receptor Complex: Binds to a tripartite receptor (CNTFRα, LIFR, gp130) to mediate signaling .
Metabolic Remodeling in the Striatum
Lentiviral-mediated overexpression of rCNTF in the rat striatum caused:
| Metabolite | Change | Mechanism |
|---|---|---|
| N-acetyl-aspartate (NAA) | ↓19% | Reduced neuronal activity |
| Glutamate (Glu) | ↓18% | Astrocyte-mediated uptake |
| Total choline (tCho) | ↑33% | Astrocyte proliferation |
| Glutamine (Gln) | ↓14% | Altered glutamate cycling |
Source:
Implications: CNTF-induced metabolic shifts may reflect compensatory mechanisms rather than neuronal loss, challenging traditional biomarker interpretations .
Retinal Degeneration Models
Intraocular rCNTF implants:
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Cone Photoreceptor Regeneration: Restores outer segment length in early-stage retinal degeneration .
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Vision Impairment: Higher doses in normal rats reduce visual acuity, highlighting dose-dependent effects .
Applications in Preclinical Research
Challenges and Considerations
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Species-Specific Activity: Human and rat CNTF differ in receptor binding efficacy due to single-residue substitutions (e.g., Arg63 vs. Gln63) .
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Purification and Stability:
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Clinical Relevance: While preclinical studies show promise, phase I trials in humans (e.g., Huntington’s disease) have faced challenges with delivery and efficacy .
Product Specs
Product Science Overview
Ciliary Neurotrophic Factor (CNTF) is a polypeptide hormone and neurotrophic factor primarily involved in the nervous system. It promotes neurotransmitter synthesis and neurite outgrowth in certain neuronal populations, including astrocytes . The recombinant version of CNTF, particularly the rat recombinant with a His tag, is widely used in research to study its effects and potential therapeutic applications.
CNTF is a member of the cytokine family and is encoded by the CNTF gene. The protein is a potent survival factor for neurons and oligodendrocytes, which are crucial for the maintenance and repair of the nervous system . The His tag, a sequence of histidine residues, is added to the recombinant protein to facilitate its purification and detection.
CNTF has several biological activities, including:
- Neuroprotection: CNTF prevents the degeneration of motor axons after axotomy (nerve injury) and supports the survival of various neuronal cell types .
- Neurogenesis: It promotes the growth and differentiation of neurons, aiding in the development and repair of the nervous system .
- Anti-inflammatory Effects: CNTF may reduce tissue destruction during inflammatory attacks, making it a potential therapeutic agent for neuroinflammatory diseases .
The rat recombinant CNTF with a His tag is used in various research applications, including:
- Neurodegenerative Disease Models: Studying the effects of CNTF in models of diseases like amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS).
- Neuronal Development Studies: Investigating the role of CNTF in the growth and differentiation of neurons.
- Drug Development: Exploring CNTF as a potential therapeutic agent for neurodegenerative and neuroinflammatory diseases.
