This project aims to evaluate the contribution of the different cerebellar cell types to neurodegeneration in ARSACS. In our recent publication (Del Bondio et al., 2023) we showed that in the ARSACS mouse cerebellum there is increased expression of astrocytic and microglial genes, supporting an inflammatory response taking place alongside the death of Purkinje cells (PCs), the most vulnerable and affected neurons in ARSACS patients and mouse models. In this project, we will employ single nuclei RNA sequencing (snRNAseq) in cerebellum, that can determine the expression level of genes within every isolated cell of the cerebellar tissue, providing the gene expression patterns specific to the different cell types in ARSACS. The analysis will be performed in the mouse model and in post-mortem ARSACS human cerebellum, and datasets compared.   Moreover, we will focus on the microglial profile of the human and mouse samples, to better investigate its role in disease progression. This human-mouse approach represents a promising opportunity to have a comprehensive view of ARSACS pathogenesis and to identify biomarkers of disease progression and novel potential targets for therapy.

Grant: $100,000

Duration : one year


Dr. Francesca Maltecca

Ospedale San Raffaele

Via Olgettina 60,20132, Milan, Italy