Spatial multi-omics reveals region-specific molecular signatures in a 6-OHDA model of Parkinson's disease.
Spatial multi-omics reveals region-specific molecular signatures in a 6-OHDA model of Parkinson's disease.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Daejeon, KR · Author affiliation
Nanobio Measurement Group, Division of Biomedical Metrology, Korea Research Institute of Standards and Science, Daejeon, Republic of Korea.Location evidence
Seoul, KR · Author affiliation
Bio-MAX Institute, Seoul National University, Seoul, Republic of Korea.Location evidence
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Original abstract
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.