Cortistatin (CORT)

Cortistatin is a cyclic neuropeptide hormone highly homologous to somatostatin, encoded by the CORT gene and predominantly expressed in the cerebral cortex and some peripheral tissues[1][2]. It is synthesized as a precursor (prepro-cortistatin) that is cleaved to active forms, mainly cortistatin-14 and cortistatin-29[1]. Cortistatin binds with nearly equal affinity to all five somatostatin receptor subtypes (SSTR1-5), which are G protein-coupled receptors involved in inhibitory neurotransmission, but unlike somatostatin, cortistatin also activates the ghrelin receptor (GHSR/GRLN-R)[4]. Cortistatin has distinct physiological roles including reducing neuronal excitability, modulating sleep and locomotor activity, suppressing pro-inflammatory cytokine production, and affecting endocrine function such as growth hormone release[7][1][2]. Preclinical evidence indicates disease relevance in inflammatory conditions (e.g., inflammatory bowel disease), neurologic diseases (e.g., epilepsy, ischemic injury), and potentially neurodegeneration[6][7][2]. While no approved drugs specifically target cortistatin, its close pharmacology with somatostatin analogues and its interaction with multiple receptor systems make it a potential therapeutic target for inflammation, neuroprotection, and hormone-related conditions[7][3][5].

Other names

Cortistatin-14Cortistatin-17Cortistatin-29CST-14CST-17CST-29prepro-cortistatinpreprocortistatinUNQ307/PRO350MGC32686

Agonist or ligand at somatostatin receptors (SSTR1-5); Agonist at ghrelin receptor (GRLN-R/GHSR); Inhibition of inflammatory cytokine production; Reduction in neuronal excitability via receptor-mediated signaling