Melanocortin 4 receptor (MC4R) (MC4R)

The Melanocortin 4 receptor (MC4R) is a G protein-coupled receptor (GPCR) that serves as a primary molecular target for the synthetic peptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro) [1][2]. While originally identified as specific binding sites in the rat basal forebrain, these sites have been characterized as high-affinity receptors that mediate the peptide's neuroprotective and nootropic effects [1]. MC4R is widely expressed in the central nervous system and is involved in regulating energy balance, but its activation by Semax specifically triggers the release of neurotrophic factors such as Brain-Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) [3][4]. This signaling cascade enhances synaptic plasticity and neuronal survival, making it a significant target for treating ischemic stroke and cognitive decline [2][5]. Drugs interacting with this receptor, including Semax and other melanocortin analogs, are used to modulate neuroplasticity and provide neuroprotection during acute brain injury [4][5]. In addition to its role in the basal forebrain, MC4R is a critical regulator of appetite and metabolism, which has led to the development of agonists for treating genetic forms of obesity [5].

Other names

MC4-RMelanocortin receptor 4Semax binding siteACTH(4-10) binding siteSpecific Semax binding sites in rat basal forebrain membranes

Agonism of the melanocortin 4 receptor (MC4R) leads to the activation of adenylyl cyclase, increasing intracellular cAMP levels and subsequently inducing the expression of neurotrophic factors like BDNF and NGF [1][3].