About PSPN / Persephin:
The main function of Persephin (also known as PSPN) is to promote and support the survival of motor neurons, ureteric bud branching and ventral midbrain dopaminergic neurons. It is related to the transforming growth factor family, which also includes neurturin, artemin and part of the GDNF (glial cell line-derived neurotrophic factor) family of ligands. They all share structural homology which makes them key factors in the survival of neuron populations, locus coeruleus noradrenergic neurons and other CNS neurons. They are also all neurotrophic factors, which are a set of small proteins and peptides which help to grow and regenerate neurons, and are essential to both the central and secondary nervous systems.
Persephin and GDNF have been considered in the application of therapeutic treatments for Parkinson’s and Alzheimer's Disease due to its ability to promote the survival of the neurons. Although it has been tested on humans (as well as rodents) and it has shown promising positive results, demonstrating neurodegeneration, it is still under surveillance and is not a definitive treatment. It is therefore evident that if a patient does have such a condition, using a medicine which includes Persephin should be thoroughly considered and its application studied before doing so.
In terms of its structure, Persephin is a complex factor within the GDNF family which is still under the process of being examined. Although they have been claims made about its neurotrophic therapeutic potential, in the growth factors of neuronal atrophy and in cellular and gene transplantation therapies for conditions such as Huntington’s disease, it’s clear that it is something that has not yet thoroughly been defined and will need to be continually studied when linking it with the treatment of conditions. However, early scientific studies in mice have shown Persephin’s potential to promote the survival of mouse embryonic basal forebrain cholinergic neurons; which in theory could have the potential to help treat Alzheimer’s disease in humans. Other studies have found that it may have clinical applications in treating other brain-related conditions; such as stroke.
The family in which Persephin exists has yet to also have a detailed mechanism created including the process, activation and secretion of them. There are a number of tissues and cells that can mature GDNF by secreting proGDNF – which in turn indicates that they can occur within the extracellular matrix, which is a structural scaffold; which is responsible for cell adhesion as well as migration, cellular growth, metabolism and other differentiation signals. Persephin’s exact mechanism is still cause for scientific study and research, and has yet to be definitively mapped; however, as its three-dimensional structure has been likened to GDNF and ARTN, is can be potentially theorised that they could have similar mechanisms, although this has not been proved.
In terms of the interactions, it’s clear that there have been studies undertaken detailing that when GDNF binds to a receptor, the region in turn then binds heparin (which is a glycosaminoglycan) which then results in a stabilizing of the structure. This directly interacts with the extracellular matrix.