Neuropeptide Y receptor type 2 (NPY2R) (NPY2R)

Neuropeptide Y receptor type 2 (NPY2R) is a G protein-coupled receptor that plays a pivotal role in regulating neuronal excitability within the central nervous system (UniProt P49146). It is predominantly expressed on presynaptic terminals, where its activation by Neuropeptide Y (NPY) leads to the inhibition of excitatory neurotransmitter release, such as glutamate. This inhibitory signaling is a natural defense mechanism against the hyperexcitability characteristic of epileptic seizures (PubMed: 25681317). In patients with drug-resistant focal epilepsy, the CG01 gene therapy utilizes an adeno-associated virus (AAV) vector to deliver the genes for both NPY and NPY2R directly to the seizure focus. This approach enhances the endogenous inhibitory pathway, allowing for localized seizure suppression that is triggered by the pathological activity itself (CombiGene, 2023). Consequently, NPY2R serves as a therapeutic target for restoring the balance between excitation and inhibition in the brain, offering a potential alternative for patients who do not respond to conventional pharmacological treatments.

Other names

NPY2-RY2 receptorNeuropeptide Y receptor Y2

CG01 is an adeno-associated virus (AAV) vector-based gene therapy that delivers the genes for both neuropeptide Y (NPY) and its Y2 receptor (NPY2R) directly into the epileptic focus. Upon expression, NPY is released during periods of high neuronal activity (seizures) and binds to the overexpressed NPY2R on presynaptic terminals. This activation inhibits the release of the excitatory neurotransmitter glutamate, thereby suppressing further seizure activity and restoring the balance between excitation and inhibition (CombiGene, 2023; Woldbye et al., 2022).