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.
Protein Name
Platelet-Derived Growth Factor Receptor Alpha (PDGFRA)
Molecular Weight
~180 kDa
Subcellular Localization
Cell Surface, Early Endosomes
Protein Family
PDGF Receptor Family (Type III RTK)
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 1. In the nervous system, PDGFRA marks neural crest-derived cells and certain glial progenitors, playing important roles in gliogenesis and white matter maintenance 2.
PDGFRA is a type I transmembrane receptor with the following domain architecture 3:
- 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
PDGFRA signaling regulates cell proliferation, migration, and survival during development and tissue repair 4:
- Glial progenitor marking: PDGFRA+ cells represent a major population of oligodendrocyte precursor cells (OPCs) in the adult brain 5
- Oligodendrocyte development: Essential for proliferation and survival of OPCs during development and remyelination
- Pericyte function: Regulates pericyte recruitment and blood-brain barrier maintenance
- Neuronal support: Paracrine signaling from PDGFRA+ cells supports neuronal health
PDGFRA activation triggers multiple downstream pathways:
- PI3K/Akt: Cell survival and metabolism
- MAPK/ERK: Cell proliferation
- PLC-gamma: Calcium signaling and cytoskeletal reorganization
- PDGFRA+ progenitor cells may contribute to dopaminergic neuron support
- Altered PDGF signaling in the substantia nigra of PD patients 6
- PDGF-based therapies being explored for neuroprotection
- PDGFRA+ OPCs are targets for remyelination therapies
- Failure of PDGF signaling may contribute to failed remyelination in MS lesions 7
- PDGF-AA delivery being investigated as a remyelination strategy
- Altered glial progenitor function in ALS
- PDGF signaling influences motor neuron environment
- Some studies suggest PDGFRA variants may influence ALS risk
- PDGFRA is overexpressed in certain cancers (GIST, glioblastoma)
- Activating mutations in PDGFRA cause gastrointestinal stromal tumors (GIST)
- Target for tyrosine kinase inhibitors
| 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 |
- 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/)
- 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.
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.
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- 1 Fredriksson et al. (2004) PDGF: A key cytokine. Ann Neurol 56:1-29.
- 2 Fruttiger et al. (1999) PDGF-A is required. Development 126:457-467.
- 3 UniProt P16234 - PDGFRA Human
- 4 Heldin & Westermark (1999) Mechanism of PDGF signaling. Physiol Rev 79:1283-1316.
- 5 Nishimura et al. (2003) PDGFRA in OPC development. J Cell Biol 163:1213-1223.
- 6 Wachnowsky et al. (2011) PDGF in PD. J Neural Transm 118:1045-1053.
- 7 Miron et al. (2013) PDGF in remyelination. Nat Neurosci 16:1211-1218.
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