1. An update on cellular and molecular determinants of Parkinson's disease with emphasis on the role of the retromer complex
- Author
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Luz-María Fuentealba, Vania Macías-Calvio, and Maria Paz Marzolo
- Subjects
0301 basic medicine ,Vacuolar protein sorting ,Retromer ,Endosome ,Pars compacta ,Neurodegeneration ,Vesicular Transport Proteins ,Parkinson Disease ,Substantia nigra ,Biology ,medicine.disease ,Cell biology ,Retromer complex ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,VPS35 ,030104 developmental biology ,0302 clinical medicine ,Mutation ,medicine ,Animals ,Humans ,030217 neurology & neurosurgery - Abstract
Parkinson's disease (PD) is a highly prevalent neurodegenerative condition. The disease involves the progressive degeneration of dopaminergic neurons located in the substantia nigra pars compacta. Among late-onset, familial forms of Parkinson are cases with mutations in the PARK17 locus encoding the vacuolar protein sorting 35 (Vps35), a subunit of the retromer complex. The retromer complex is composed of a heterotrimeric protein core (Vps26-Vps35-Vps29). The best-known role of retromer is the retrieval of cargoes from endosomes to the Golgi complex or the plasma membrane. However, recent literature indicates that retromer performs roles associated with lysosomal and mitochondrial functions and degradative pathways such as autophagy. A common point mutation affecting the retromer subunit Vps35 is D620N, which has been linked to the alterations in the aforementioned cellular processes as well as with neurodegeneration. Here, we review the main aspects of the malfunction of the retromer complex and its implications for PD pathology. Besides, we highlight several controversies still awaiting clarification.
- Published
- 2020
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