PDGF Signaling Pathway: A Drug Target for Neurological Disorders

Target Name: PTN

NCBI ID: G5764

Content of Review Report on PTN Target / Biomarker

PTN

PDGF Signaling Pathway: A Drug Target for Neurological Disorders

Platelet-derived neurotrophic factor (PDGF) is a protein that plays a crucial role in the development and maintenance of neural tissue, including brain. PDGF is a transmembrane glycoprotein that consists of a cytoplasmic tail and a transmembrane domain. One of the PDGF islet, PDGF-BB (Platelet-derived brain-derived neurotrophic factor), has been shown to have neuroprotective effects in various neurological disorders such as Alzheimer's disease, Parkinson's disease, and chronic pain.

PDGF signaling pathway

PDGF signaling pathway is a complex intracellular signaling pathway that involves the interactions between various proteins, including tyrosine kinases, phosphatidylinositol (PI) receptors, and transcription factors. The PDGF signaling pathway is involved in the regulation of cell proliferation, differentiation, and survival.

PDGF signaling pathway has three main components: the tyrosine kinase receptor, the intracellular signaling pathway, and the downstream signaling pathway. The tyrosine kinase receptor is the protein that binds PDGF and triggers the intracellular signaling pathway. The intracellular signaling pathway involves the interactions between the tyrosine kinase receptor, phosphatidylinositol (PI) receptors, and transcription factors. Finally, the downstream signaling pathway involves the interactions between the intracellular signaling pathway and the downstream signaling pathway.

PDGF signaling pathway is involved in the regulation of cell proliferation, differentiation, and survival. It plays a crucial role in the development and maintenance of neural tissue, including the brain. PDGF signaling pathway is also involved in the regulation of pain perception and neuroprotection.

Drug targeting PDGF signaling pathway

PDGF signaling pathway is a drug target of interest in the development of new treatments for various neurological disorders. The use of PDGF inhibitors has been shown to have neuroprotective effects in various neurological disorders, including Alzheimer's disease, Parkinson's disease, and chronic pain.

PDGF-BB, a variant of PDGF, has been shown to have neuroprotective effects in various neurological disorders. Studies have shown that PDGF-BB can increase the levels of brain-derived neurotrophic factor (BDNF) in the brain, which is a protein that plays a role in the regulation of neural plasticity. Additionally, PDGF-BB can also inhibit the activity of the transcription factor, NF-kappa-B, which is involved in the regulation of pain perception.

PDGF-BB has also been shown to have anti-inflammatory effects, as it can reduce the levels of pro-inflammatory cytokines in the brain. Additionally, PDGF-BB can also increase the levels of neuroprotective enzymes, such as superoxide dismutase (SOD), which is involved in the regulation of oxidative stress.

Conclusion

PDGF signaling pathway is a drug target of interest in the development of new treatments for various neurological disorders. The use of PDGF inhibitors, such as PDGF-BB, has been shown to have neuroprotective effects in various neurological disorders. Further studies are needed to fully understand the mechanisms of PDGF signaling pathway and its potential as a drug target.

Protein Name: Pleiotrophin

Functions: Secreted growth factor that mediates its signal through cell-surface proteoglycan and non-proteoglycan receptors (PubMed:16814777, PubMed:11278720, PubMed:19141530). Binds cell-surface proteoglycan receptor via their chondroitin sulfate (CS) groups (PubMed:26896299, PubMed:27445335). Thereby regulates many processes like cell proliferation, cell survival, cell growth, cell differentiation and cell migration in several tissues namely neuron and bone (PubMed:1733956, PubMed:1768439, PubMed:11278720, PubMed:19141530, PubMed:27445335, PubMed:30667096, PubMed:19442624). Also plays a role in synaptic plasticity and learning-related behavior by inhibiting long-term synaptic potentiation (By similarity). Binds PTPRZ1, leading to neutralization of the negative charges of the CS chains of PTPRZ1, inducing PTPRZ1 clustering, thereby causing the dimerization and inactivation of its phosphatase activity leading to increased tyrosine phosphorylation of each of the PTPRZ1 substrates like ALK, CTNNB1 or AFAP1L2 in order to activate the PI3K-AKT pathway (PubMed:17681947, PubMed:27445335, PubMed:30667096, PubMed:16814777, PubMed:10706604). Through PTPRZ1 binding controls oligodendrocyte precursor cell differentiation by enhancing the phosphorylation of AFAP1L2 in order to activate the PI3K-AKT pathway (PubMed:27445335, PubMed:30667096). Forms a complex with PTPRZ1 and integrin alpha-V/beta-3 (ITGAV:ITGB3) that stimulates endothelial cell migration through SRC dephosphorylation and activation that consequently leads to ITGB3 'Tyr-773' phosphorylation (PubMed:19141530). In adult hippocampus promotes dendritic arborization, spine development, and functional integration and connectivity of newborn granule neurons through ALK by activating AKT signaling pathway (By similarity). Binds GPC2 and chondroitin sulfate proteoglycans (CSPGs) at the neuron surface, leading to abrogation of binding between PTPRS and CSPGs and neurite outgrowth promotion (By similarity). Binds SDC3 and mediates bone formation by recruiting and attaching osteoblasts/osteoblast precursors to the sites for new bone deposition (By similarity). Binds ALK and promotes cell survival and cell proliferation through MAPK pathway activation (PubMed:11278720). Inhibits proliferation and enhances differentiation of neural stem cells by inhibiting FGF2-induced fibroblast growth factor receptor signaling pathway (By similarity). Mediates regulatory mechanisms in normal hemostasis and in hematopoietic regeneration and in maintaining the balance of myeloid and lymphoid regeneration (By similarity). In addition may play a role in the female reproductive system, auditory response and the progesterone-induced decidualization pathway (By similarity)

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•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
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•   the target screening and validation;
•   expression level;
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•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
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•   advantages and risks of development, etc.
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