Determination of the pharmacological properties of a novel angiotensin analogue in NG108-15 cells

@Academia in Neurology , in Neurosurgery , in Trauma and Orthopaedics
  • Pre-clinical research (Blizard Institute) View on Map
  • Posted On : 30/05/2022
  • Application Deadline or Event Date : 27/06/2022
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  • Training Stage Suitability Junior Medical Student Senior Medical Student
  • Location Suitability candidates nationally
  • Category Research or Audit or QI Projects

Project Description

Recent results have proposed that the selective activation of the angiotensin 2 (AII) receptor (AT2R) could be a novel drug target in the treatment of brain ischemia and neurotrauma. This strategy improves functional recovery through neuroprotective and anti-apoptotic mechanisms and increased axonal plasticity in experimental animal models of spinal cord injury and traumatic brain injury.

Because AT1R activation is considered harmful in stroke, Alzheimer’s disease, Parkinson’s disease, depression, and bipolar disorder, stimulation of AT2R with an agonist of very high selectivity over AT1R will have high therapeutic potential in various neurological and psychiatric conditions. We have previously reported that a novel AT2R peptide agonist showing an 18,000 times higher selectivity for AT2R over AT1R (compound 2) enhanced neurite growth (50 ± 10%) in mouse embryonic cortical neurons. We now have available an improved agonist with the best AT2R over AT1R selectivity reported so far in the literature (33,000 times), along with 3 other novel compounds. We will explore their pharmacological properties and efficacy for neuroregeneration in cortical cell and neuroblastoma x glioma hybrid NG108-15 cell culture (these cells only express the AT2R subtype under certain culture conditions). The novel agonists will be tested against AII and the AT2R antagonist EMA401.

This project will provide skills and knowledge in cell culture techniques, in vitro pharmacology, immunocytochemistry, high-throughput image acquisition (using the IN Cell Analyzer 2200) and analysis (using the IN Carta analysis software), manipulation of large data files, graphing and statistical analysis. If the student is not available to physically join in the lab they could still be involved in image analysis, data handling, graphing, and statistical analysis.

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