Leucine‐rich repeat kinase 2 and lysosomal dyshomeostasis in Parkinson disease

Cogo, S., Manzoni, C., Lewis, P. A. and Greggio, E. (2020) Leucine‐rich repeat kinase 2 and lysosomal dyshomeostasis in Parkinson disease. Journal of Neurochemistry, 152 (3). pp. 273-283. ISSN 1471-4159 doi: 10.1111/jnc.14908

Abstract/Summary

Over the last two decades, a number of studies have underlined the importance of lysosomal-based degradative pathways in maintaining the homeostasis of post-mitotic cells, and revealed the remarkable contribution of a functional autophagic machinery in the promotion of longevity. In contrast, defects in the clearance of organelles and aberrant protein aggregates have been linked to accelerated neuronal loss and neurological dysfunction. Several neurodegenerative disorders, among which Alzheimer disease (AD), Frontotemporal dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS) to name a few, are associated with alterations of the autophagy and endo-lysosomal pathways. In Parkinson disease (PD), the most prevalent genetic determinant, Leucine-rich repeat kinase 2(LRRK2), is believed to be involved in the regulation of intracellular vesicle traffic, autophagy and lysosomal function. Here, we review the current understanding of the mechanisms by which LRRK2 regulates lysosomal-based degradative pathways in neuronal and non-neuronal cells and discuss the impact of pathogenic PD mutations in contributing to lysosomal dyshomeostasis.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/87298
Item Type	Article
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > Department of Chemistry
Uncontrolled Keywords	Biochemistry, Cellular and Molecular Neuroscience
Publisher	Wiley
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