369. Proteomic Signatures of Health and Aging.

Abstract Abstract Text: Mass spectrometry-based proteomics has become a cornerstone technology in biological and biomedical research by enabling the comprehensive analysis of thousands of proteins, their modifications and interactions in a single experiment. Because proteins are the cellular workhorse, proteomics provides a powerful window into the molecular mechanisms underlying health, aging, and disease, while also revealing biomarkers and therapeutic targets. In this presentation, I will summarize advanced proteomics approaches and illustrate how mass spectrometry-based proteomics signatures can be used to better understand complex biological processes in health and diseases. I will highlight recent results from my laboratory on aging and Parkinson’s disease caused by A53T alpha-synuclein mutation. Although the accumulation of alpha-synuclein is a hallmark of Parkinson’s disease, the molecular mechanisms and pathways driving disease progression remain poorly understood. Using transgenic mouse model carrying human A53T alpha-synuclein mutation and advanced proteomics, we have revealed widespread remodeling of proteins involved in mitochondrial function, glutamate signaling, synaptic transmission, and metabolic pathways, together with the accumulation of stress-related and aggregation-associated proteins. Proteins responsible for protein quality control, immune regulation, and lysosomal function were broadly reduced, suggesting impaired cellular defense mechanisms. Integrated proteomic, metabolomic, and lipidomic analyses further revealed coordinated changes in energy metabolism, membrane lipids, and neuronal signaling that accompany disease progression. Together, these findings demonstrate how proteomics can uncover molecular signatures that define health and disease, provide new insights into disease processes, and identify potential biomarkers and therapeutic targets for precision medicine.