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

AbstractOver 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 a ccelerated 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 Park inson 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.

Source: Journal of Neurochemistry - November 5, 2019 Category: Neuroscience Authors: Susanna Cogo, Claudia Manzoni, Patrick A. Lewis, Elisa Greggio Tags: Review Source Type: research