Evaluation of therapeutic strategies to slow down neurodegeneration in experimental models of spinocerebellar ataxia type 1

The project aims at studying the potential therapeutic effects of Dasatinib, Quercetin and RO0711401 in an experimental model of spinocerebellar ataxia type 1 (SCA1) by using a high-sensitivity microscopic approach based on X-ray phase-contrast micro-CT (X-PCI-CT) for multiscale, post-mortem 3D virtual-histology. Neuroprotection is demanded in neurodegenerative disorders such as SCA1, but to date no treatment is currently available. SCA1 is a dominantly inherited genetic disease due to an increase in the number of CAG repeats in the ATXN1 gene leading to an expanded polyQ tract in the ataxin-1 protein, and degeneration of cerebellar Purkinje cells (PC). The expanded ataxin-1 protein forms toxic aggregates, likely the major cause of neuronal cell death. Senescence and reduction of mGlu1 metabotropic glutamate receptors are involved in neurodegeneration. Targeting senescent cells or mGlu1 receptors could be potential disease modifying treatments for neurodegenerative disorders.