Dott. Elia Di Schiavi

Institute of Biosciences and BioResources, IBBR-CNR-Napoli

 

Seminario: “Identification of neuroprotective genes and drugs using a new C. elegans SMA model“.

19/10/2021

Abstract: 

Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by the selective degeneration of lower spinal cord motor neurons, which leads to progressive muscle atrophy and death of young patients. SMA is caused by mutations of the Survival of Motor Neuron gene, Smn1, a ubiquitous gene with housekeeping functions, but the molecular mechanisms underlying SMA remain to be understood. To elucidate the molecular basis of SMA and identify potential therapeutic molecules we took advantage of a new C.elegans SMA model we developed. In the absence of a specific molecular target, chemical and genetic screens can be performed using small model systems that can, at the same time, elucidate the molecular mechanisms underlying the disease and identify new drugs. C. elegans represents one of these valuable model organisms for human diseases, since its genome encodes many human disease orthologs and the biological processes are very well conserved. Importantly, the use of C.elegans allows to strongly reduce the number of vertebrate animals used, in compliance with Italian and international guidelines, fulfilling the 3Rs principles. Thus we developed an innovative genetic model, which enabled us to efficiently reduce the function of smn-1 gene, the C.elegans homolog of Smn1, specifically in 19 motor neurons. The specific silencing of smn-1 causes an age-dependent neurodegeneration that results in altered locomotion and in neuronal degeneration and death. These results provide strong evidence that this is a powerful and unique tool to study SMA, that allows both the study of the neurodegeneration process in vivo and the test of new therapeutics. In the talk I will present how we used this model for unbiased genetic and drug screenings and the results recently obtained.

 

 

INFO : seminari.irib@irib.cnr.it