Neurotrophic Factors

Neurotrophin 4 (NTF4), also known as NT5, is a member of the NGF family of neuronal and epithelial growth factors. Neurotrophins have six conserved cysteine residues that are involved in the formation of three disulfide bonds. Human NT4 shares 48 - 52% amino acid sequence identity with human β-NGF, BDNF and NT3. It shares 91% and 95% amino acid sequence identity with mouse and rat NT4/5, respectively. The protein is secreted as a homodimer and can also form heterodimers with BDNF or NT3. NT4 binds and induces receptor dimerization and activation of TrkB and promotes the development and survival of selected peripheral and CNS neurons. NT4 induced TrkB signaling augments NMDA receptor activity and increases neuronal sensitivity to excitotoxic cell death. NT4 is secreted by activated T cells and granulocytes and contributes to tissue regeneration at inflammation sites.

Persephin (PSPN) belongs to the GDNF ligand subfamily of the TGF-beta superfamily. The amino acid sequence of human PSPN is about 30% analogous to human GDNF. PSPN is synthesized throughout the nervous system and presumably originates from both astroglial cells and neurons. It promotes the survival and growth of mesencephalic dopaminergic and motor neurons. It also plays a role in kidney development by promoting ureteric bud branching. PSPN binds to a receptor complex consisting of Ret tyrosine kinase and GFR-alpha-4.

Persephin (PSPN) belongs to the GDNF ligand subfamily of the TGF-beta superfamily. The amino acid sequence of PSPN exhibits significant homology to GDNF. PSPN is synthesized throughout the nervous system and presumably originates from both astroglial cells and neurons. It promotes the survival and growth of mesencephalic dopaminergic and motor neurons. It also plays a role in kidney development by promoting ureteric bud branching. PSPN binds to a receptor complex consisting of Ret tyrosine kinase and GFR-alpha-4.

Pleiotrophin (PTN) is a heparin-binding protein, expression of which is developmentally regulated. It is expressed primarily in brain tissues, but is also expressed in lung, kidney, gut, and bone tissues and can be induced by PDGF. PTN is expressed in some tumor cells as well. PTN is involved in a diverse array of functions including mitogenesis, angiogenesis, tissue repair, and neurite outgrowth. It exhibits strong mitogenic activity towards hepatocytes and plays a role in liver regeneration. PTN binds to several different receptors including syndecan-3, PTP-zeta, and ALK. The nucleotide sequence of Human pleiotrophin is about 50% homologous to human midkine (MDK).