New publication - DOPAL initiates αSynuclein-dependent impaired proteostasis and degeneration of neuronal projections in Parkinson’s disease.

Pubblicato il: 14.04.2023 11:41

The misfolding and aggregation of αSynuclein (αSyn) constitutes a driving factor in synaptic derangement, leading to degeneration of the dopaminergic neurons in Parkinson’s disease (PD). In the work published in npj Parkinson’s Disease (https:// doi.org/10.1038/s41531-023-00485-1) coordinated by Anna Masato (PhD at DiBio UNIPD, now post-doc at University College London), Luigi Bubacco (DiBio UNIPD) and Daniela Boassa (University California San Diego), the authors untangled the impact of the reactive dopamine catabolite DOPAL as trigger of αSyn-mediated neurotoxicity. By combining biochemical, cellular and imaging techniques, they demonstrated that DOPAL-induced αSyn aggregation affects synaptic integrity, challenges protein quality control machineries in the neuronal projections and reduces axonal arborization. Thanks to the collaborations with Randy Strong (University of Texas San Antonio) and Luisa Dalla Valle (DiBio UNIPD), these observations were substantiated in mouse and zebrafish in vivo models. Finally, in partnership with Abcam, a novel antibody against DOPAL-modified αSyn has been generated and tested in post-mortem brain tissues from PD patients, corroborating the translational relevance of the DOPAL-αSyn neurotoxic interplay in PD pathogenesis.