Cellular and Molecular Neurobiology
Author: Tomás Eidelman | email: tomas.eidelman@gmail.com
Tomás Eidelman 1°, Hernán Ezequiel Hauché Pedernera 1°, Oscar Samuel Gershanik 3°, Maria Elena Avale 2°, Melina Paula Bordone 1°, Juan Esteban Ferrario 1°
1° Laboratorio de Neurobiología de la Enfermedad de Parkinson, IB3, UBA-CONICET Ciudad Autónoma de Buenos Aires, Argentina
2° Laboratorio de Terapéutica Experimental en Procesos Neurodegenerativos ,INGEBI-CONICET Ciudad Autónoma de Buenos Aires, Argentina.
3° Universidad Favaloro, Ciudad Autónoma de Buenos Aires, Argentina.
Regulation of gene expression using the RNA interference (RNAi) technology is a promising therapeutical approach with real perspective for clinical translation.Several clinical trials are already in progress but none of them was proved to tackle brain diseases yet. In our laboratory, we have developed an RNAi against the mRNA of the tyrosine kinase fyn aimed to reduce the levodopa induced dyskinesia in Parkinsons disease (PD). Combined with lentiviral delivered into the striatum, we have reduced dyskinesia in a pre-clinical model of PD mice (Bordone et al 2021). Although viral transduction was restricted only to the infected areas, fyn expression is ubiquitous throughout the brain and then we envisage to develop further precision of silencing among neuronal subtypes. We designed a molecular scalpel to provide a fine therapeutic option that shall reduce side effects. To reach this goal we have designed a strategy using a modified Cre-LoxP system to restrict expression of RNA molecules into dopamine D1R-expressing neurons. We have cloned the synapsin promoter inverted between lox71/lox66 sequences upstream a EGFP reporter, that should only express in the presence of the recombinase Cre. The next step is to go forward with the already validated miRNA against Fyn. In this poster we will discuss our strategy, show the first trials in vitro and in vivo to evaluate the correct functioning of the system, and the following steps towards testing its efficacy in a mouse model of LID.