School of Basic Pharmaceutical and Toxicological Sciences, University of Louisiana Monroe, Monroe, LA, USA.
Endocrine, Polypeptide, and Cancer Institute, Veterans Affairs Medical Center, University of Miami, Miami, FL, USA.
Horm Metab Res. 2020 May;52(5):336-339. doi: 10.1055/a-1149-9347. Epub 2020 May 13.
Growth hormone releasing hormone is a hypothalamic neuropeptide, which regulates the release of growth hormone from the anterior pituitary gland. Growth hormone releasing hormone antagonists are anticancer agents, associated with strong anti-inflammatory activities. In the present study, we investigated the effects of the GHRH antagonist MIA-602 in the integrity of the brain microvascular endothelium in vitro. Our observations suggest that MIA-602 protects against the HO-induced breakdown of the brain endothelium and enhances its integrity by inducing P53, deactivating cofilin, and suppressing the RhoA inflammatory pathway. Thus, GHRH antagonists may offer an exciting possibility for the treatment of pathologies related to the blood brain barrier dysfunction, including the Parkinson's and Alzheimer's diseases.
生长激素释放激素是一种下丘脑神经肽,可调节生长激素从前垂体的释放。生长激素释放激素拮抗剂是一种抗癌药物,具有很强的抗炎活性。在本研究中,我们研究了 GHRH 拮抗剂 MIA-602 对体外脑微血管内皮完整性的影响。我们的观察表明,MIA-602 通过诱导 P53、失活 cofilin 和抑制 RhoA 炎症途径,可防止 HO 诱导的脑内皮破裂,并增强其完整性。因此,GHRH 拮抗剂可能为治疗与血脑屏障功能障碍相关的疾病提供了一种令人兴奋的可能性,包括帕金森病和阿尔茨海默病。