NEUROTROPHIN-3, HUMAN

Description

Neurotrophin-3 is the third neurotrophic factor, characterized after nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). NT-3 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. NT-3 also binds to TrkA, TrkB, and p75NTR with low affinity. NT-3 promotes the differentiation, growth, and survival of neurons. The distribution of NT-3 and its biological activity on a variety of neuronal populations clearly distinguish NT-3 from NGF and BDNF, indicating that NT-3 is an authentic neurotrophic factor that has its own characteristic role in vivo.

General Description

NT-3 (neurotrophin 3) is a neurotrophic factor 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 systems and can signal through the trk receptors. Recombinant human NT-3 is a noncovalently linked homodimer, of two 13.6kDa polypeptide monomers (240 total amino acid residues). The amino acid sequences of human, murine and rat NT-3 are identical.

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.