Contribution of Autophagy-Lysosomal Pathway in the Exosomal Secretion of Alpha-Synuclein and Its Impact in the Progression of Parkinson's Disease

Denisse Sepúlveda; Marisol Cisternas-Olmedo; Javiera Arcos; Melissa Nassif; René L Vidal

doi:10.3389/fnmol.2022.805087

Contribution of Autophagy-Lysosomal Pathway in the Exosomal Secretion of Alpha-Synuclein and Its Impact in the Progression of Parkinson's Disease

Front Mol Neurosci. 2022 Feb 17:15:805087. doi: 10.3389/fnmol.2022.805087. eCollection 2022.

Authors

Denisse Sepúlveda^{1

2

3}, Marisol Cisternas-Olmedo^{1

2

3}, Javiera Arcos^{1

2

3}, Melissa Nassif^{1

4}, René L Vidal^{1

2

3}

Affiliations

¹ Center for Integrative Biology, Facultad de Ciencias, Universidad Mayor, Santiago, Chile.
² Biomedical Neuroscience Institute, University of Chile, Santiago, Chile.
³ Geroscience Center for Brain Health and Metabolism, Santiago, Chile.
⁴ Escuela de Biotecnología, Facultad de Ciencias, Universidad Mayor, Santiago, Chile.

Abstract

Parkinson's disease (PD) is caused by the degeneration of dopaminergic neurons due to an accumulation of intraneuronal abnormal alpha-synuclein (α-syn) protein aggregates. It has been reported that the levels of exosomal α-syn of neuronal origin in plasma correlate significantly with motor dysfunction, highlighting the exosomes containing α-syn as a potential biomarker of PD. In addition, it has been found that the selective autophagy-lysosomal pathway (ALP) contributes to the secretion of misfolded proteins involved in neurodegenerative diseases. In this review, we describe the evidence that supports the relationship between the ALP and α-syn exosomal secretion on the PD progression and its implications in the diagnosis and progression of this pathology.

Keywords: Parkinson’s disease progression; autophagy-lysosomal pathway; biomarker; degradation; α-syn exosomal secretion.

Publication types

Review