To develop novel CRF1 receptor inhibitors is important to treat neuropsychiatric disorders

According to research using recombinant dog proteins, CRF mRNA and CRF are widely distributed in the central nervous system (CNS) and abundant in the hypothalamic paraventricular nucleus (PVN), brainstem, amygdala, hippocampus and neocortex. CRF is a neuropeptide containing 41 amino acids. It is a kind of hormone that regulates the hypothalamic-pituitary-adrenal (HPA) axis of the hypothalamus. It is also the key hormone of neuroendocrine regulation in stress response.

CRF receptors are mainly two seven transmembrane G protein receptors (CRF1, CRF2). CFR and CFR1 have high affinity, but the affinity for CFR2 is weak. In the human body, CFR1 includes five subtypes of α, b, c-h, i, mainly distributed in the anterior pituitary, hippocampus, cerebral cortex and amygdala. Distribution of CFR1 in the anterior pituitary promotes the release of adrenocorticotropic hormone (ACTH) in the hypothalamus, which in turn promotes the release of cortisol from the adrenal cortex; which in turn regulates glucocorticoid receptors (GRs) and mineralocorticoid receptor (MRs) and the signal cascade mediates intracellular responses to stress.

Compared to CRF1, CRF2 is confined to discrete brain regions, such as the dorsal raphe nucleus (DRN), lateral septa (LS), and periaqueductal gray (PAG). CRF2 only has three subtypes: a, b, c. Although the role of CRF2 is less than CRF1, it can antagonize the CRF1-induced stress response. The different roles of CRF1 and CRF2 are also reflected in the distribution of DRN nerve cells. CRF1 is mainly in the cell membrane, while CRF2 is mainly distributed in the cytoplasm. Tension stimulation reverses this distribution, causing CRF to stimulate DRN cells rather than inhibition.

CRF1 and CRF2 have a variety of signaling pathways, the main pathway is CRF1 and CRF2 triggering downstream cascade signals leading to G protein activation, Gαs trigger second messenger cAMP (cyclization of monophosphate), cAMP activation of cAMP protein kinase A (protein kinase A, PKA). They also activate Gαq, activating the cascade of protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) - mitogen-activated protein kinase (MAPK). They can also activate the apoptotic pathway through Akt / protein kinase B, NOS-guanylate cyclase and caspase. Because of this complexity, CRF1 may exchange signals through different channels of the signal.

With the further development of psychopathology, the role of CRF gets more and more attention. Numerous studies have shown that CRF levels are high in patients with neuropsychiatric disorders (including depression, addiction disorder, post-traumatic stress disorder, irritable bowel syndrome, generalized anxiety disorder, etc.) and they also found CRF mRNA increase in the tissues in patients. Subsequent studies have shown that patients are over-expressed in CRF mRNA, resulting in excessive production of CRF. Other studies have demonstrated that increased activity of the CRF1 receptor leads to the development of certain neuropsychiatric disorders. At the same time, it was also demonstrated that specific SNPs are also associated with depression. Therefore, to develop novel CRF1 receptor inhibitors is important for the treatment of neuropsychiatric disorders. Flarebio provides you with good-quality recombinant proteins including recombinant ECE1.