Leucine‐rich repeat kinase 2 and lysosomal dyshomeostasis in Parkinson disease. Issue 3 (24th November 2019)

• Record Type: Journal Article
• Authors: Cogo, Susanna; Manzoni, Claudia; Lewis, Patrick A.; Greggio, Elisa
• Is Part Of: Journal of neurochemistry. Volume 152:Issue 3(2020)
• Page Start: 273
• Page End: 283
• Publication Date: 2019-11-24
• Subjects: glia -- immunity -- LRRK2 -- lysosomal‐degradation -- neurons -- Parkinson disease; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.14908
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract: 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, and Amyotrophic Lateral Sclerosis 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. Abstract : Several neurodegenerative disorders are associated with alterations in the autophagy and endo‐lysosomal pathways. In Parkinson disease, mounting evidence links Leucine‐rich repeat kinase 2 (LRRK2) to intracellular vesicle traffic, autophagy and lysosomal function. In this review, we discuss the rapidly increasing roles proposed for LRRK2 at the intersection with lysosome biology and how disease‐associated mutations affect lysosomal‐based degradative pathways in neuronal and non‐neuronal cells.