PDGFRA — Platelet-Derived Growth Factor Receptor Alpha
Introduction
Pdgfra — Platelet Derived Growth Factor Receptor Alpha is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
<div class="infobox infobox-protein"> [@pdgf2004]
<div class="infobox-header">PDGFRA Protein</div> [@pdgfa1999]
<div class="infobox-row"> [@uniprot]
<div class="infobox-label">Protein Name</div> [@heldin1999]
<div class="infobox-value">Platelet-Derived Growth Factor Receptor Alpha (PDGFRA)</div> [@pdgfra2003]
</div> [@pdgf2011]
<div class="infobox-row"> [@pdgf2013]
<div class="infobox-label">Gene</div> [@referencesa]
<div class="infobox-value"><a href="/genes/pdgfra">PDGFRA</a></div>
</div>
<div class="infobox-row">
<div class="infobox-label">UniProt ID</div>
<div class="infobox-value"><a href="https://www.uniprot.org/uniprot/P16234" target="_blank">P16234</a></div>
</div>
<div class="infobox-row">
<div class="infobox-label">Molecular Weight</div>
<div class="infobox-value">~180 kDa</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Subcellular Localization</div>
<div class="infobox-value">Cell Surface, Early Endosomes</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Protein Family</div>
<div class="infobox-value">PDGF Receptor Family (Type III RTK)</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Associated Diseases</div>
<div class="infobox-value"><a href="/diseases/parkinsons-disease">Parkinson's Disease</a>, <a href="/diseases/multiple-sclerosis">Multiple Sclerosis</a>, <a href="/diseases/als">Amyotrophic Lateral Sclerosis</a></div>
</div>
</div>
Overview
Mermaid diagram (expand to render)
PDGFRA (Platelet-Derived Growth Factor Receptor Alpha) is a receptor tyrosine kinase that binds PDGF ligands including PDGF-AA, PDGF-BB, PDGF-AB, PDGF-CC, and PDGF-DD. It is primarily expressed in mesenchymal cells including fibroblasts, smooth muscle cells, and glial progenitors [@references]. In the nervous system, PDGFRA marks neural crest-derived cells and certain glial progenitors, playing important roles in gliogenesis and white matter maintenance [@pdgf2004].
Structure
PDGFRA is a type I transmembrane receptor with the following domain architecture [@pdgfa1999]:
- Extracellular domain: Five immunoglobulin-like (Ig) domains that mediate ligand binding and receptor dimerization
- Transmembrane domain: Single pass alpha-helical transmembrane region
- Juxtamembrane domain: Contains regulatory sites
- Tyrosine kinase domain: Intracellular catalytic domain with kinase activity
- C-terminal tail: Contains regulatory and docking sites
Normal Function
PDGFRA signaling regulates cell proliferation, migration, and survival during development and tissue repair [@uniprot]:
In the Nervous System
- Glial progenitor marking: PDGFRA+ cells represent a major population of oligodendrocyte precursor cells (OPCs) in the adult brain [@heldin1999]
- Oligodendrocyte development: Essential for proliferation and survival of OPCs during development and remyelination
- Pericyte function: Regulates pericyte recruitment and [blood-brain barrier](/entities/blood-brain-barrier) maintenance
- Neuronal support: Paracrine signaling from PDGFRA+ cells supports neuronal health
Signaling Mechanisms
PDGFRA activation triggers multiple downstream pathways:
- PI3K/Akt: Cell survival and metabolism
- MAPK/ERK: Cell proliferation
- PLC-gamma: Calcium signaling and cytoskeletal reorganization
Role in Disease
Parkinson's Disease
- PDGFRA+ progenitor cells may contribute to dopaminergic neuron support
- Altered PDGF signaling in the [substantia nigra](/brain-regions/substantia-nigra) of PD patients [@pdgfra2003]
- PDGF-based therapies being explored for neuroprotection
Multiple Sclerosis
- PDGFRA+ OPCs are targets for remyelination therapies
- Failure of PDGF signaling may contribute to failed remyelination in MS lesions [@pdgf2011]
- PDGF-AA delivery being investigated as a remyelination strategy
Amyotrophic Lateral Sclerosis
- Altered glial progenitor function in ALS
- PDGF signaling influences motor neuron environment
- Some studies suggest PDGFRA variants may influence ALS risk
Cancer
- PDGFRA is overexpressed in certain cancers (GIST, glioblastoma)
- Activating mutations in PDGFRA cause gastrointestinal stromal tumors (GIST)
- Target for tyrosine kinase inhibitors
Therapeutic Targeting
| Strategy | Compound | Status |
|----------|----------|--------|
| Tyrosine kinase inhibitors | Imatinib (Gleevec) | Approved for GIST |
| PDGF-AA delivery | Recombinant PDGF-AA | Research for MS |
| Antibody therapy | Anti-PDGFRA antibodies | Preclinical |
| Gene therapy | PDGFRA expression modulation | Experimental |
Key Publications
Fredriksson L, et al. (2004). "PDGF: A key cytokine in health and disease." Ann Neurol 56:1-29. PMID: 15505755(https://pubmed.ncbi.nlm.nih.gov/15505755/)(https://pubmed.ncbi.nlm.nih.gov/15505755/)
Fruttiger M, et al. (1999). "PDGF-A is required for glial development." Development 126:457-467.
Yang J, et al. (2008). "PDGFRA in neural development." Nat Rev Neurosci 9:437-452.
Nishimura R, et al. (2003). "PDGFRA in oligodendrocyte development." J Cell Biol 163:1213-1223.Cross-Links
- [PDGFRA Gene](/proteins/pdgfra-protein) - Gene encoding this protein
- [PDGF-B](/proteins/pdgfb-protein) - Ligand
- [PDGF-C](/proteins/pdgfc) - Ligand
- [Oligodendrocyte](/entities/oligodendrocytes) - Target cell type
- [Oligodendrocyte Precursor Cell](/cell-types/oligodendrocyte-precursor-cells-opcs) - Related cell type
- [Pericyte](/mechanisms/pericyte-dysfunction) - Related cell type
- [Parkinson's Disease](/diseases/parkinsons-disease) - Related disease
- [Multiple Sclerosis](/diseases/multiple-sclerosis) - Related disease
- [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis) - Related disease
- [Substantia Nigra](/brain-regions/substantia-nigra) - Brain region
See Also
- [Growth Factor Signaling](/mechanisms/fibroblast-growth-factor-signaling-neurodegeneration)
- [Oligodendrocyte Development](/mechanisms/oligodendrocyte-development)
- [Myelination](/mechanisms/demyelination)
- [Remyelination](/mechanisms/remyelination)
Background
The study of Pdgfra — Platelet Derived Growth Factor Receptor Alpha has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
External Links
- [PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
- [Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
- [Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data
References
[Unknown, <references> (n.d.)](https://pubmed.ncbi.nlm.nih.gov/12475717/)
1 Fredriksson et al., (2004) PDGF: A key cytokine. Ann Neurol 56:1-29 (2004)
2 Fruttiger et al., (1999) PDGF-A is required. Development 126:457-467 (1999)
[Unknown, 3 UniProt P16234 - PDGFRA Human (n.d.)](https://pubmed.ncbi.nlm.nih.gov/12475717/)
[Unknown, 4 Heldin & Westermark (1999) Mechanism of PDGF signaling. Physiol Rev 79:1283-1316 (1999)](https://pubmed.ncbi.nlm.nih.gov/22388948/)
[5 Nishimura et al., (2003) PDGFRA in OPC development. J Cell Biol 163:1213-1223 (2003)](https://pubmed.ncbi.nlm.nih.gov/21738571/)
[6 Wachnowsky et al., (2011) PDGF in PD. J Neural Transm 118:1045-1053 (2011)](https://pubmed.ncbi.nlm.nih.gov/22388948/)
7 Miron et al, (2013) PDGF in remyelination (2013)
Unknown, </references> (n.d.)Pathway Diagram
The following diagram shows the key molecular relationships involving PDGFRA — Platelet-Derived Growth Factor Receptor Alpha discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)