Neuroprotective Proteins in Hypoxia-stressed Astrocyte-Derived Extracellular Vesicles

Background: Mass spectrometry-based proteomic analysis advancements have generated extensive protein data from cells involved in neurodegenerative diseases. The field of neuroproteomics is expanding to include the study of extracellular vesicles (EVs) to identify potential biomarkers for disease prevention and endogenous factors involved in neuroprotection. Methods: In this study, the cortical astrocytes in normoxia were cultured and subjected to hypoxic conditions and obtained astrocyte-derived EVs released in supernatant separately then performed label- free mass spectrometry-based proteomics of these EVs to determine which is the effect of the hypoxic event on the cargo proteins. A meta-analysis of the results compared with previously published databases was conducted. Data was deposited in the ProteomeXchange Consortium with the identified PXD050160. Results: This study revealed a differential expression of 83 upregulated proteins under hypoxic conditions and 61 downregulated proteins under normoxic conditions, highlighting the protective protein signatures elicited by astrocytes. Conclusion: The present study makes a novel contribution by employing proteomic techniques to characterize the protein cargo of EVs isolated from primary rat astrocytes. This approach allows for a more refined analysis of astrocyte-specific intercellular signaling under hypoxic conditions. It offers valuable insights into the roles of astrocytes in maintaining brain homeostasis and contributing to pathological processes.