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Caught in the act: LRRK2 in exosomes
1Duke Center for Neurodegeneration and Neurotherapeutics, Duke University, Durham, NC 27710, U.S.A.
Biochemical Society Transactions
|March 7, 2019
Summary
Mutations in leucine-rich repeat kinase 2 (LRRK2) are linked to Parkinson's disease. LRRK2 protein is found in exosomes, offering potential for disease diagnosis and therapy.
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are a common genetic cause of late-onset Parkinson's disease (PD).
- LRRK2 protein plays a role in cellular vesicle trafficking, including endosomal and lysosomal pathways.
- Extracellular vesicles, specifically exosomes, can package and transport LRRK2 protein outside the cell.
Purpose of the Study:
- To review the biology of exosome-associated LRRK2.
- To explore the potential utility of exosome-associated LRRK2 in Parkinson's disease diagnosis, prognosis, and theranosis.
Main Methods:
- Literature review of studies investigating LRRK2 protein, exosomes, and Parkinson's disease.
- Analysis of LRRK2's role in vesicle trafficking and its presence in exosomes.
- Examination of disease-linked modifications and stability of exosomal LRRK2.
Main Results:
- LRRK2 protein is packaged into exosomes, which are secreted into biofluids.
- Exosomal LRRK2 can carry disease-linked post-translational modifications.
- Exosomal LRRK2 is relatively stable in the extracellular environment.
Conclusions:
- Exosome-associated LRRK2 represents a promising biomarker for Parkinson's disease.
- LRRK2 within exosomes may serve diagnostic, prognostic, and therapeutic roles in LRRK2-linked diseases.
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