Microtubule Destabilization Is Shared by Genetic and Idiopathic Parkinson’s Disease Patient Fibroblasts

摘要: Data from both toxin-based and gene-based models suggest that dysfunction of the microtubule system contributes to pathogenesis Parkinson’s disease, even if, at present, no evidence alterations microtubules in vivo or patients is available. Here we analyze cytoskeleton organization primary fibroblasts deriving with idiopathic genetic focusing on mutations parkin leucine-rich repeat kinase 2. Our analyses reveal likely pathology affects cytoskeletal stability, without any activation autophagy apoptosis. All parkinsonian have a reduced mass, represented by higher fraction unpolymerized tubulin respect control cells, display significant changes stability-related signaling pathways. Furthermore, show reduction mass so closely related alteration cell morphology behavior pharmacological treatment microtubule-targeted drugs, approaches, transfecting wild type 2, restore proper stability are able rescue architecture. Taken together, our results destabilization point convergence forms parkinsonism highlight, for first time, occurs not only experimental disease. Therefore, these data contribute knowledge molecular cellular events underlying disease and, revealing correction defects restores phenotype, may offer new therapeutic target management