Often abbreviated to PTN and known under an array of names including neurite growth-promoting factor 1 (NEGF1) due to the scientists that discovered it, it is a protein that exists within humans that is linked with the PTN gene. A protein which has a high affinity for heparin (a medication which is used as a blood thinner) it has a 18-kDa growth factor. It stimulates neural development, hematopoietic stem cell maintenance and cell differentiation.
PTN has often been linked to neurodegenerative disorders as it provides trophic support and promotes positive recovery. There have been numerous studies over the years on rats, in which PTN-treated cells were grafted into the striatum of rats that had Parkinson's Disease. From these experiments, it became clear that blocking the RPTPζ/β through this method could be a way of treating the neurodegenerative disease. It can also be directly linked to HIV, as a way of inhibiting the disease through binding with nucleolin – acting as a low-affinity receptor. A fascinating protein that is continuously studied in both humans and animals, its structure, interactions, function and mechanisms are incredibly complex.
Pleiotrophin is structurally related to both heparin-binding protein and midkine. It has a high percentage of amino acid residues that results in an anomalous migration. Its structure varies on whether it is within an adult or a child and will develop over the course of the years.
When Pleiotrophin is linked with midkine, it can create a series of regulated heparin-binding proteins. Present within the peripheral and central nervous system (in the early stages of embryonic as well as postnatal development), as well as within the gut, bone and kidney (amongst other non-neural tissues), it is an essential protein within the body. In adults, it sits within the hippocampus in the brain and can be linked to tumour angiogenesis. It is a vital cell-signalling cytokine that’s needed for development.
Pleiotrophin Mechanisms and Interactions
There are a variety of mechanisms that Pleiotrophin has within the body. One of which is the mechanism created by the interaction between PTM and NRP-1. Demonstrating how the protein assists with cancer progression and tumour angiogenesis, it controls the tumoral cell and endothelial response.
Secondly, PTN is known to regulate the production of cytokines and help with preventing inflammation. The mechanisms taken to achieve this were written about in a study conducted by scientists in a French laboratory - “In the present study, we show for the first time that PTN induces the expression of inflammatory cytokines including TNF-alpha, IL-1beta and IL-6 in quiescent human peripheral blood mononuclear cells (PBMC)”.
In terms of interactions, Pleiotrophin directly interacts with Glycosaminoglycan as well as a variety of ECM cells. It also links with chondroitin sulfate proteoglycan and tyrosine phosphatase zeta which is a receptor-type protein in order to promote angiogenic activities. Pleiotrophin has a range of functions and interactions which make it vital within the nervous system. A secreted growth factor, it will be continued to be studied for years to come due to its importance.