Premium
Leucine‐rich repeat kinase 2 and lysosomal dyshomeostasis in Parkinson disease
Author(s) -
Cogo Susanna,
Manzoni Claudia,
Lewis Patrick A.,
Greggio Elisa
Publication year - 2020
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14908
Subject(s) - lrrk2 , autophagy , frontotemporal dementia , microbiology and biotechnology , lysosome , parkinson's disease , biology , amyotrophic lateral sclerosis , neuroscience , leucine rich repeat , kinase , lewy body , intracellular , disease , dementia , medicine , biochemistry , apoptosis , pathology , enzyme
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.