Spatial multi-omics reveals region-specific molecular signatures in a 6-OHDA model of Parkinson’s disease

Le résumé fourni par la source

Parkinson's disease (PD) is characterized by complex molecular and circuit-level alterations that extend beyond dopaminergic neurodegeneration, yet the spatial integration of metabolic and proteomic changes remains insufficiently explored. Here, we combined time-of-flight secondary ion mass spectrometry-based metabolite imaging with laser cell sorting proteomics to interrogate molecular alterations in the substantia nigra and striatum of the 6-hydroxydopamine toxin model of PD. Our analyses revealed distinct region-specific metabolic and proteomic signatures within primary lesion sites, and additionally uncovered unexpected and widespread off-target changes across neural circuits. These findings demonstrate that even in a toxin-induced model, PD pathology involves extensive reorganization of molecular networks and circuit-level processes, underscoring the complexity and diffuseness of disease mechanisms. By applying a spatially resolved, multilayered approach, this study expands the pathophysiological understanding of PD and provides a foundation for future investigations into the spatial and temporal dynamics of neurodegenerative disease progression.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.