## Neuropilin-1 is a protein encoded by the [NRP1](/genes/nrp1) gene that nrp1 plays essential roles in:. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
## Neuropilin-1 is a protein encoded by the [NRP1](/genes/nrp1) gene that nrp1 plays essential roles in:. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
Neuropilin-1 (NRP1) is a transmembrane glycoprotein (923 amino acids) with an extracellular domain containing:
Two CUB domains (a1/a2) - bind semaphorins
Two coagulation factor V/VIII homology domains (b1/b2) - bind VEGF
A MAM domain (c) - involved in dimerization
A short cytoplasmic tail with a PDZ-binding motif
NRP1 functions as a co-receptor for both VEGF and semaphorin ligands, forming complexes with tyrosine kinase receptors (VEGFR1/2) and plexin receptors.
Normal Function
NRP1 plays essential roles in:
Angiogenesis: Forms complexes with VEGFR2 to enhance VEGF signaling and promote blood vessel formation
Axonal guidance: Acts as a semaphorin 3A receptor to repel axons during development
Immune response: Modulates T-cell activation and dendritic cell function
Synaptogenesis: Regulates formation and maintenance of excitatory synapses
Cell survival: Activates downstream signaling through PI3K/Akt and MAPK pathways
Role in Neurodegeneration
Alzheimer's Disease
NRP1 is implicated in AD pathogenesis through multiple mechanisms:
VEGF-NRP1 signaling: Reduced NRP1 expression impairs cerebral angiogenesis and [blood-brain barrier](/entities/blood-brain-barrier) integrity in AD
[Aβ](/proteins/amyloid-beta) interaction: Aβ peptides bind NRP1 and disrupt normal VEGF signaling
Synaptic dysfunction: NRP1 deficiency leads to impaired synaptic plasticity and memory deficits
Neuroinflammation: NRP1 modulates microglial activation and neuroinflammatory responses
Genetic studies: NRP1 polymorphisms associated with AD risk in certain populations