130939-66-1

Basic information

• Product Name: NEUROTROPHIN-3, HUMAN
• Synonyms: HUMAN NERVE GROWTH FACTOR-2;HUMAN NT-3;HUMAN NGF-2;HUMAN NEUROTROPHIN 3;HUMAN NEUROTROPHIC FACTOR;HUMAN NEUROTROPHIC FACTOR-3;HUMAN HGNF;NT-3
• CAS NO: 130939-66-1
• Molecular Weight: 0
• Mol File: 130939-66-1.mol
• Article Data: 0

Chemical Properties

• Appearance: /lyophilized powder
• Storage Temp.: −20°C
• CAS DataBase Reference: NEUROTROPHIN-3, HUMAN(CAS DataBase Reference)
• NIST Chemistry Reference: NEUROTROPHIN-3, HUMAN(130939-66-1)
• EPA Substance Registry System: NEUROTROPHIN-3, HUMAN(130939-66-1)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 130939-66-1(Hazardous Substances Data)

Usage

Description

Neurotrophin-3, Human (NT-3) is a neurotrophic factor that is structurally related to β-NGF (nerve growth factor), BDNF (brain-derived neurotrophic factor), and NT-4. These proteins belong to the cysteine-knot family of growth factors that assume stable dimeric structures. NT-3 is expressed by neurons of the central nervous system and can signal through the trk receptors. It is a polypeptide consisting of 119 amino acid residues and forms a homodimer. NT-3 binds to tropomyosin receptor kinase C (TrkC) with high affinity and also binds to TrkA, TrkB, and p75NTR with low affinity. NT-3 promotes the differentiation, growth, and survival of neurons, playing a characteristic role in the nervous system.

Uses

Used in Pharmaceutical Industry:
Neurotrophin-3, Human is used as a therapeutic agent for promoting the differentiation, growth, and survival of neurons. Its high affinity for TrkC and low affinity for TrkA, TrkB, and p75NTR make it a valuable target for the development of treatments for various neurological disorders and injuries.
Used in Research and Development:
Neurotrophin-3, Human is used as a research tool for studying the biological activity and mechanisms of action of neurotrophic factors. It can be employed in in vitro and in vivo experiments to investigate the effects of NT-3 on neuronal differentiation, growth, and survival, as well as its interactions with various trk receptors.
Used in Drug Delivery Systems:
Neurotrophin-3, Human can be incorporated into drug delivery systems to enhance its therapeutic potential and bioavailability. By developing novel drug delivery systems, such as nanoparticles or other carriers, the delivery, efficacy, and targeting of NT-3 to specific neuronal populations can be improved, potentially leading to more effective treatments for neurological conditions.
Used in Neuroregeneration and Repair:
Neurotrophin-3, Human is used as a regenerative agent for promoting the repair and regeneration of damaged neurons. Its role in neuronal differentiation, growth, and survival makes it a promising candidate for the development of treatments aimed at restoring neuronal function and structure in cases of injury or disease.
Used in Neuroprotection:
Neurotrophin-3, Human is used as a neuroprotective agent for safeguarding neurons from damage and degeneration. By promoting the survival and growth of neurons, NT-3 may help to protect against the loss of neuronal function and structure in various neurodegenerative conditions.

Discovery

By the 1980s, NGF and BDNF had been isolated and characterized. The structural similarity between NGF and BDNF and their restricted neuronal specificity suggest that additional and functionally distinct members of this family might exist. Then, taking advantage of sequence identities between NGF and BDNF and polymerase chain reaction, Hohn et al. identified a third member of this family, named neurotrophin-3 (NT-3) in 1990. Within 3 months after the publication of the study, five studies on the cloning and identification of NT-3 were published.

Structure

NT-3 is a polypeptide consisting of 119 aa residues. The human NTF3 gene encodes a preproprotein of 257 aa residues (preproNT-3) . After cleavage, the mature NT-3 dimerizes through noncovalent interaction.?NT-3 has been identified in mammals, birds, reptiles, amphibians, and teleosts. The amino acid sequences of NT-3 are highly conserved among vertebrates. Mammalian NT-3 has 100% homology. Six cysteines involved in the intramolecular disulfide bond are conserved among all vertebrate NT-3s.

Properties

Mr. 27,453 (mammalian preproNT-3); 13,625 (mammalian mature NT-3). pI=9.3. NT-3 is soluble in water. Disulfide bridges are formed between Cys14 and Cys79, between Cys57 and Cys108, and between Cys67 and Cys110 (in mammalian mature NT-3).

Gene, mRNA, and precursor

The human proNT-3 gene, NTF3, location 12p13.31, consists of three exons. The human NT-3 mRNA has 1182 bases that encode a preproNT-3 of 257 aa residues.?ProNT-3 shows broad expression in the ovary (RPKM 4.8), spleen (RPKM 2.1), and 19 other tissues including the heart, liver, pancreas, kidney, and brain. In the brain, higher levels of expression are observed in the hippocampus, cerebellum, olfactory bulb, and septam.

Receptors

NT-3 binds to tropomyosin receptor kinase C (TrkC) with high affinity, and to TrkA, TrkB, and p75NTR with low affinity. These receptors are singletransmembrane receptors. Unlike TrkA, TrkB, and p75NTR, TrkC binds specifically to NT-3. The human NTRK3 gene encodes TrkC of 839 aa residues. The human NGFR gene encodes p75NTR of 427 aa residues. TrkC has a tyrosine-kinase domain in the cytoplasmic region. There are truncated isoforms lacking the tyrosine-kinase domain. p75NTR has no tyrosine-kinase domain. The binding activity of mature NT-3: Kd=10 pM (TrkC) and 1 nM (p75NTR).

Biological functions

TrkC shows a biased expression in the brain (RPKM 2.8), the fat (RPKM 1.2), and 13 other tissues, including the endometrium and testis. Prominent expression of TrkC gene is observed in the hippocampus, cerebral cortex, and the granular cell layer of the cerebellum. The activation of TrkC promotes the survival and differentiation of existing neurons and the growth and differentiation of new neurons. NT-3 also enhances synaptic transmission in the rat hippocampal slices. The role of p75NTR in NT-3 signaling is less clear.

Biochem/physiol Actions

NT-3 (neurotrophin 3) promotes the growth and survival of nerve and glial cells. It is associated with neuroprotection and polymorphisms in the gene are associated with risk to Alzheimer′s disease. It is also linked with attention-deficit/hyperactivity disorder (ADHD) and mood disorders. NT-3 enhances the metastatic proliferation of breast cancer cells in the brain.

Clinical Use

NT-3 shows protective effects against acoustic neurotoxicity by aminoglycoside antibiotics. Currently, NT-3 is being investigated in clinical trials as a treatment for peripheral neuropathies, including Charcot-Marie Tooth neuropathy, and it is also expected to be useful in the treatment of injured spinal cords.