Neurotrophin-4 (NT-4), also known as NT-4/5 or NT-5, is a member of the neurotrophin family of proteins, which are essential for the development, function, and survival of neurons. The neurotrophin family includes other well-known proteins such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3). Neurotrophins play a crucial role in the nervous system by promoting the growth, differentiation, and survival of neurons.
NT-4 is a homodimeric protein, meaning it consists of two identical subunits. It is produced as a precursor protein that undergoes proteolytic cleavage to generate the mature, biologically active form. The mature NT-4 protein is approximately 14 kDa in size and is characterized by a conserved cysteine knot structure, which is a hallmark of the neurotrophin family.
NT-4 exerts its biological effects by binding to specific receptors on the surface of target cells. The primary receptor for NT-4 is the tropomyosin receptor kinase B (TrkB), a receptor tyrosine kinase. Upon binding to TrkB, NT-4 induces receptor dimerization and autophosphorylation, leading to the activation of downstream signaling pathways that promote neuronal survival, differentiation, and growth. Additionally, NT-4 can bind to the p75 neurotrophin receptor (p75NTR), which modulates the activity of TrkB and influences the cellular response to NT-4.
NT-4 is expressed in a variety of tissues and cell types, including neuronal cells, normal breast epithelial cells, melanocytes, activated T cells, and granulocytes . Its expression is regulated by various factors, including neuronal activity and injury. In the nervous system, NT-4 is produced by both neurons and glial cells, and it acts in a paracrine or autocrine manner to support neuronal function and survival.
The biological activity of NT-4 has been extensively studied in various experimental models. NT-4 promotes the survival and differentiation of sensory neurons, motor neurons, and dopaminergic neurons. It also enhances synaptic plasticity, which is essential for learning and memory. In addition to its neurotrophic effects, NT-4 has been shown to modulate immune responses and promote the survival of non-neuronal cells, such as melanocytes and breast epithelial cells .
Recombinant human NT-4 (hNT-4) is produced using recombinant DNA technology, typically in bacterial or mammalian expression systems. The recombinant protein is purified to high purity and is biologically active, retaining the ability to bind to TrkB and activate downstream signaling pathways. Recombinant hNT-4 is widely used in research to study the mechanisms of neurotrophin signaling and to develop potential therapeutic applications for neurodegenerative diseases, nerve injuries, and other conditions that affect the nervous system .
Recombinant hNT-4 has several applications in both basic research and clinical settings. In research, it is used to investigate the signaling pathways and cellular responses mediated by NT-4 and its receptors. It is also employed in studies aimed at understanding the role of neurotrophins in neuronal development, synaptic plasticity, and neuroprotection.
In the medical field, NT-4 has potential therapeutic applications for the treatment of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, as well as for promoting nerve regeneration following injury. Additionally, NT-4 may have applications in the treatment of certain cancers, given its ability to support the survival and function of non-neuronal cells .