Novel dimers as inhibitors of alpha-synuclein aggregation
Date
2022
Authors
Ruiz, Priscila
Krol, Ed
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
Type
Poster Presentation
Degree Level
Abstract
Parkinson’s Disease is characterized by the death of dopaminergic neurons in the substantia nigra as a result of the aggregation of alpha synuclein (AS)
Nicotine from smoking and 1 aminoindan (a metabolite of Rasagiline) seem to be neuroprotective compounds and both have been associated with the reduction of the risk to develop Parkinson’s disease
These compounds bind to AS at both the N and C terminus, forcing the protein to adopt a loop conformation, which appear to contribute to the neuroprotective activity of the drugs
Dimer molecules linked with two neuroprotective compounds should increase the binding constants to AS and increase the efficacy to prevent AS aggregation
Phase 1 metabolic studies using hepatic microsomes in vitro are needed to determine the susceptibility of the compounds to biotransformation
Description
Keywords
Parkinson's disease, drug discovery