What is it about?
Parkinson’s disease is a serious condition, and scientists are looking for ways to understand and treat it better. One key protein involved in Parkinson’s is called PARK7/DJ-1, which is found in higher levels in the blood and other fluids of people with various diseases, making it a potential marker for diagnosis. Our study demonstrated that PARK7 is secreted from cells through an unconventional pathway. When cells are stressed, particularly by a toxin that mimics Parkinson’s, PARK7 is processed through the cell’s recycling system and then released using specific proteins.
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Why is it important?
This study is significant because it reveals, for the first time, the detailed mechanism by which PARK7 is secreted from cells under oxidative stress. By identifying the involvement of macroautophgay, chaperone-mediated autophagy, and dedicated SNARE proteins, we provide a deeper understanding of how this protein, which is crucial in multiple diseases, is regulated. Since PARK7 is found in extracellular fluids in disease states, understanding its secretion could lead to new diagnostic tools or therapeutic strategies. For instance, modulating PARK7 secretion might help in managing Parkinson’s disease or other conditions where PARK7 levels are altered. Moreover, this research contributes to the broader field of cell biology by elucidating an unconventional secretion pathway, which could have implications for other proteins that use similar mechanisms. The use of 6-OHDA, a neurotoxin relevant to Parkinson’s, also highlights the study’s relevance to neurodegenerative diseases.
Perspectives
As researchers, we are excited about this discovery because it not only advances our understanding of PARK7’s biology but also opens up new research avenues. We hope that this work will inspire further studies on the extracellular functions of PARK7 and how its secretion is regulated in different disease contexts. In the future, we plan to investigate whether this secretion mechanism is conserved across different cell types and to explore potential ways to manipulate it for therapeutic purposes.
Biplab Kumar Dash
Doshisha University
Read the Original
This page is a summary of: Unconventional secretion of PARK7 requires lysosomal delivery via chaperone-mediated autophagy and specialized SNARE complex, Proceedings of the National Academy of Sciences, May 2025, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2414790122.
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