GHRH Antagonists Protect Against Hydrogen Peroxide-Induced Breakdown of Brain Microvascular Endothelium Integrity.
Barabutis. Nektarios N; Akhter. Mohammad S MS; Uddin. Mohammad A MA; Kubra. Khadeja-Tul KT; Schally. Andrew V AV
Key Findings
- MIA‑602 prevented H2O2‑induced breakdown of brain microvascular endothelial cells in vitro
- The protection involved increased p53 activity, deactivation of cofilin, and suppression of the RhoA inflammatory pathway
- GHRH antagonists are proposed as potential treatments for blood‑brain barrier dysfunction
Practical Outcomes
- For biohackers using sermorelin (a GHRH agonist), this study doesn’t provide a direct protocol or dosage change. It does highlight that modulating the GHRH system can impact brain vascular health, but the benefits were seen with an antagonist in a cell model, so more research is needed before any real‑world application.
Summary
A lab study found that a GHRH‑blocking molecule called MIA‑602 can shield brain blood‑vessel cells from damage caused by hydrogen peroxide, a type of oxidative stress. It does this by turning on protective proteins (like p53) and turning off inflammation‑related pathways (RhoA, cofilin). The authors suggest this could help conditions where the blood‑brain barrier breaks down, such as Alzheimer’s or Parkinson’s disease.
Abstract
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 H<sub>2</sub>O<sub>2</sub>-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.
Study Information
pubmed
2020
2020-05-13T00:00:00.000Z
10.1055/a-1149-9347
22
20