Cellular and Molecular Neurobiology
Author: Angela Tissone | Email: anyisone@gmail.com
Angela Isabel Tissone 1°, Joaquín Alejo Quintana 2°, Leonardo Molano Ramirez 2°, María Soledad Espósito 2°
1° Laboratorio de Neurobiología del Movimiento. Departamento de Física Médica. Centro Atómico Bariloche.
2° Laboratorio de Neurobiología del Movimiento. Departamento de Física Médica. Centro Atómico Bariloche. Comisión Nacional de Investigaciones Científicas y Técnicas. CONICET CCT Patagonia Norte
Parkinson’s disease (PD) is the second-most common neurodegenerative disorder and is characterized by a progressive multi-neuronal dysfunction originating a plethora of debilitating motor and non-motor symptoms. Two cardinal features characterized the disease: the presence of intracellular protein aggregates enriched in alpha-synuclein and the selective vulnerability to neurodegeneration of particular subsets of neuronal subtypes in specific brain regions whereas other apparently similar cells are resistant. To assess the patho-mechanism underlying selective vulnerability we developed a cell-type specific viral vector that conditionally overexpresses a mutant variant of alpha-synuclein that allows to induce synucleopathy within individual circuit elements in vivo. When delivered to dopaminergic neurons of the substantia nigra pars compacta, our approach recapitulates the main hallmarks of the disease, namely Lewy-body-like aggregation, progressive dopaminergic neuronal death and nigrostriatal projections loss. The circuit-specificity of our approach not only allow us to unveil central pathomechanisms of the disease, but also to disentangle the circuit elements underlying less studied motor and non-motor PD symptoms.