Metabotropic glutamate receptor 4 (mGluR4) (mGluR4)

Metabotropic glutamate receptor 4 (mGluR4) is a Class C G protein-coupled receptor (GPCR) that belongs to Group III of the metabotropic glutamate receptor family [1, 3, 7, 10]. It is primarily localized presynaptically in the central nervous system, particularly in the cerebellum, basal ganglia, and hippocampus, where it acts as an autoreceptor to inhibit the release of glutamate and other neurotransmitters [1, 4, 5, 15]. By modulating synaptic transmission and reducing excitotoxicity, mGluR4 plays a crucial role in maintaining neuronal homeostasis and regulating motor control and emotional states [1, 4, 5, 8]. In disease contexts, mGluR4 is a major therapeutic target for Parkinson's disease, as its activation can compensate for the overactivity of the indirect pathway in the basal ganglia [2, 4, 5, 12, 16]. It is also being investigated for its potential in treating anxiety, depression, schizophrenia, and chronic pain [1, 4, 8, 14, 16]. Pharmacological strategies primarily focus on positive allosteric modulators (PAMs), such as foliglurax, which enhance the receptor's response to endogenous glutamate [1, 4, 5, 12, 16]. While preclinical models have shown significant neuroprotective and symptomatic benefits, clinical translation has faced challenges, including achieving sufficient efficacy and managing potential central nervous system side effects like dizziness and hallucinations [4, 11, 12, 14].

Other names

GRM4GPRC1DMGLUR4mGlu4Glutamate metabotropic receptor 4

Positive allosteric modulation (PAM), Orthosteric agonism