LRRK2 and autophagy: a common pathway for disease

Abstract

LRRK2 (leucine-rich repeat kinase 2) is an enzyme implicated in human disease, containing kinase and GTPase functions within the same multidomain open reading frame. Dominant mutations in the LRRK2 gene are the most common cause of familial PD (Parkinson's disease). Additionally, in genome-wide association studies, the LRRK2 locus has been linked to risk of PD, Crohn's disease and leprosy, and LRRK2 has also been linked with cancer. Despite its association with human disease, very little is known about its pathophysiology. Recent reports suggest a functional association between LRRK2 and autophagy. Implications of this set of data for our understanding of LRRK2's role in physiology and disease are discussed in the present paper.

Exploring the “Multiple-Hit Hypothesis” of Neurodegenerative Disease: Bacterial Infection Comes Up to Bat

“…The authors proposed that loss of LRRK2 enhances M. tuberculosis phagosomal maturation, but how these cell-intrinsic differences translate to enhanced innate immune cytokine expression remains unclear. Surprisingly, the authors found no LRRK2-dependent changes to xenophagy of M. tuberculosis , despite a number of reports linking LRRK2 to mitochondrial turnover in other cell types (Manzoni, 2012). Curiously, Harlova et al also reported that macrophages harboring the PD-associated G2019S gain-of-function LRRK2 mutation supported higher levels of M. tuberculosis growth.…”

Identification of Key Genes and Pathways in Female Lung Cancer Patients Who Never Smoked by a Bioinformatics Analysis

“…Thus far, the biological functions of PPBP in lung cancer remain unclear. LRRK2 is a member of the leucine-rich repeat kinase family, and it is related to a variety of human diseases, such as Parkinson's disease, cancer, Crohn's disease and leprosy, but little know about its physiological effects 38. Both CDH5 and SELE are adhesion molecules, but the former is a classical cadherin of the cadherin superfamily and the latter is the part of the selectin family.…”

Ca2+in quality control

“…ADCY, adenylate cyclase; GNAS, GNAS complex locus; iMPA, inositol monophosphatase. study, Gómez-Suaga et al 35 concluded that the overexpression of LRRK2 (leucine-rich repeat kinase-2), mutations which cause late-onset Parkinson disease, 40 stimulate the release of Ca 2+ from lysosomal stores in human embryonic kidney cells, which in turn increases formation of autophagic vesicles. In this study autophagic induction was found to be mediated by a pathway involving CAMKK2-PRKAA but independent of MTOR.…”