Speaker: Aurora Martinez, Neuro-SysMed PI, professor at the Department of Biomedicine, University of Bergen, and leader of the Biorecognition Research Unit.
Title: Compound screening and drug discovery in Parkinson’s disease
Place: The auditorium in Armauer Hansens Hus (campus Haukeland University Hospital)
Time: Wednesday April 26 at 11:30 – 13:00 (lunch from 11:30 – 12:00).
Registration link: is available here
Lecture language: English
Abstract: Computational and experimental screenings by specific assays and subsequent optimization of selected hits are crucial activities for the discovery and development of new drugs. In the field of Parkinson’s disease (PD) and other parkinsonisms, levodopa is considered the standard medication as it is relatively effective for the management of motor dysfunction, but often presents side effects and gradually loses efficacy. There are no effective disease modifying therapies that cure or slow down PD progression, and our research group aims to contribute to the development of these highly needed therapies. One of our main approaches focuses on the discovery of pharmacological chaperones, which are small molecular weight molecules that specifically bind to protein targets and stabilize unstable and misfolded conformations, with the potential to increase the half-life and functionality of the targets. We have developed biophysical and cellular high-throughput assays for the screening of chemical libraries with diversity-compound collections, fragments, or approved drugs for the identification of stabilizing binders, with follow-up functional assays and hit expansion and optimization. Understanding the structural and regulatory determinants of the targets and their complexes with regulatory proteins largely contributes to a successful development of mechanistic therapies. Results will be presented on our results on discovery and development of pharmacological chaperones for genetic conformational disorders, and to increase cellular levels of several targets of interest in PD, such as the highly regulated tyrosine hydroxylase (TH), the vesicular monoamine transporter 2 (VMAT2) and essential components of mitochondrial function, notably Complex I.