The Neuroprotective Effects of GPR4 Inhibition through the Attenuation of Caspase Mediated Apoptotic Cell Death in an MPTP Induced Mouse Model of Parkinson’s Disease

The proton-activated G protein-coupled receptor (GPCR) 4 (GPR4) is constitutively active at physiological pH, and GPR4 knockout protected dopaminergic neurons from caspase-dependent mitochondria-associated apoptosis. This study explored the role of in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse model Parkinson’s disease (PD). In mice, subchronic MPTP administration causes oxidative stress-induced apoptosis substantia nigra pars compacta (SNpc), resulting motor deficits. NE52-QQ57, selective antagonist, reduced neuronal loss MPTP-treated improving memory functions. NE52-QQ57 co-treatment mice significantly decreased pro-apoptotic marker Bax protein levels increased anti-apoptotic Bcl-2 SNpc striatum. MPTP-induced caspase 3 activation poly (ADP-ribose) polymerase (PARP) cleavage striatum co-treated with NE52-QQ57. tyrosine hydroxylase (TH)-positive cell numbers compared alone. improved rotarod pole test–assessed performance Y-maze spatial memory. Our findings suggest may represent potential therapeutic target for PD, involved caspase-mediated mice.