Neurotrophin-4 (NT-4) belongs to a group of nerve growth factors that influence nerve cell proliferation through selective and non-covalent interactions with the nerve growth factor receptor. [1]
Function
NT-4 functions as a growth factor in many biological pathways and processes to induce neuronal proliferation. [2]
Biological Processes
Positive regulation of neurotrophin TRK receptor signaling pathway:
NT-4 functions as a ligand when binding to neurotrophin receptor tyrosine kinase NTRK2. Auto-phosphorylated NTRK2 dimers that are formed on tyrosine residues in receptor tail as a result of NT-4 binding.
Adult locomotory behavior [3], neuron projection morphogenesis:
generating projection structures of a neuron, [4]
ganglion mother cell fate determination,[5] epidermis development, [6] innervation, long term memory, [7] chemical synaptic transmission modulation and nerve development, [8] mechanoreceptor differentiation, negative regulation of neuron apoptotic process, and positive regulation of peptidyl-serine phosphorylation, [9] nerve growth signaling pathway, [10] and sensory organ boundary specification (taste bud development). [11]
Disease
NT-4, along with other growth factors including neurotrophin-3 (NT-3), brain-derived neurotrophic factor (), and nerve growth factor (NGF) have all shown to be essential for survival of neurons. [12] [13] These growth factors have been associated with parts of the cerebrum including the frontal lobe and limbic system because of their involvement in neurological processes like behavior, learning, and memory. [14] Availability and binding affinity are two factors that contribute to development of Alzheimer's disease and Huntington's disease, as well as neurodegenerative and psychiatric disorders. [15] Both increased and decreased levels of NT-4 are associated with various disease states that effect mental development and decline. Serum concentration levels of NT-4 and BDNF were found to be higher in patients with autism and in patients with mental retardation [16] Defects or mutations in NT-4 has been associated with development of glaucoma.
Relevance
NT-4 is essential for neuron survival and proliferation throughout ones life span so maintaining proper amounts in the body is needed to stay healthy. Neuron growth factors are currently being used as biomarkers to study the relationship between them and various mental disease states including depression, schizophrenia, autism, Alzheimer's and Huntington's disease. Knowing the cause of variance in these levels is key for prevention of certain neurological disorders.
Depletion and/or unavailable receptor binding sites are also being studied to further understand these mechanisms.
Structural highlights
NT-4 is a homodimer; Its includes 2 Neurotrophin-4 factors bound with a chloride ion. NT-4 is 130 amino acids in length. This chloride ion is a ligand that binds to nerve growth factor receptors.
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