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Development of Autophagy-lysosome Biomarkers for Parkinson’s Disease Using Stem Cell-derived Neurons and Biofluids

Study Rationale: Genetic, molecular, and pathological studies have highlighted the role of dysfunctional mechanisms for clearing cellular debris — called autophagy-lysosome pathways — in the development of Parkinson’s disease (PD). However, investigation of this molecular impairment, and its involvement in PD, has been limited by the lack of reliable, quantitative tests for monitoring autophagy-lysosome activity. Development of sensitive, robust autophagy-lysosome assays will be key to discovering PD biomarkers for clinical application. 

Hypothesis: We hypothesize that through our systematic search and development, we will be able to identify better molecules as a proxy for predicting autophagy-lysosome activity.

Study Design: We will leverage the findings from our previous comprehensive protein profiling of human neurons and explore a few top-ranked autophagy targets for their potential to become robust autophagy-lysosome biomarkers. Combining immunoassays with a protein-identification technique called mass spectrometry, we will measure the levels of different proteins processed by autophagy. We will then validate the use of these autophagy cargo proteins for predicting autophagy-lysosome activity in neurons produced from human stem cells and in biofluids from individuals carrying genetic variants linked to PD.

Impact on Diagnosis/Treatment of Parkinson’s disease: Our study provides an opportunity to determine new molecular biomarkers for PD progression, which is important for understanding PD subtypes, improving prognosis and stratifying volunteers for clinical trials.

Next Steps for Development: We will increase the number of human biofluid samples and test the sensitivity of the immunoassays in multiple types of human biofluid.


  • Zhenyu Yue, PhD

    New York, NY United States

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