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LRRK2 is involved in the chemotaxis of neutrophils and differentiated HL-60 cells, and the inhibition of LRRK2 kinase activity increases fMLP-induced chemotactic activity
BackgroundNeutrophils depend heavily on glycolysis for energy production under normal conditions. In contrast, neutrophils require energy supplied by...
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Pharmacology of LRRK2 with type I and II kinase inhibitors revealed by cryo-EM
LRRK2 is one of the most promising drug targets for Parkinson’s disease. Though type I kinase inhibitors of LRRK2 are under clinical trials,...
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LRRK2 phosphorylation status and kinase activity regulate (macro)autophagy in a Rab8a/Rab10-dependent manner
Mutations in the leucine-rich repeat kinase 2 ( LRRK2 ) gene are the most common genetic cause of Parkinson’s disease (PD), with growing importance...
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Sex-dependent interactions between prodromal intestinal inflammation and LRRK2 G2019S in mice promote endophenotypes of Parkinson’s disease
Gastrointestinal (GI) disruptions and inflammatory bowel disease (IBD) are commonly associated with Parkinson’s disease (PD), but how they may impact...
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Structural basis for Parkinson’s disease-linked LRRK2’s binding to microtubules
Leucine-rich repeat kinase 2 ( LRRK2 ) is one of the most commonly mutated genes in familial Parkinson’s disease (PD). Under some circumstances, LRRK2...
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Parkinson’s disease kinase LRRK2 coordinates a cell-intrinsic itaconate-dependent defence pathway against intracellular Salmonella
Cell-intrinsic defences constitute the first line of defence against intracellular pathogens. The guanosine triphosphatase RAB32 orchestrates one...
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R1441C and G2019S LRRK2 knockin mice have distinct striatal molecular, physiological, and behavioral alterations
LRRK2 mutations are closely associated with Parkinson’s disease (PD). Convergent evidence suggests that LRRK2 regulates striatal function. Here, by...
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Generation of an Induced Pluripotent Stem Cell Line, ICGi043-A, by Reprogramming Peripheral Blood Mononuclear Cells from a Parkinson’s Disease Patient with p.G2019S Mutation in the LRRK2 Gene
AbstractThe pathological variant p.G2019S in the LRRK2 gene leads to the occurrence of a hereditary form of Parkinson’s disease (PD) and affects 7%...
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An Induced Pluripotent Stem Cell Line (ICGi023-A) Obtained from a Patient with Parkinson’s Disease Associated Polymorphisms in LRRK2 and PINK1 Genes
AbstractParkinson’s disease is a neurodegenerative disease, and genetic variants are known in only 5% of cases. Analysis of clinical exome of a...
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Generation of an Induced Pluripotent Stem Cell Line, ICGi042-A, by Reprogramming Peripheral Blood Mononuclear Cells from a Parkinson’s Disease Patient with c.1000G>A Mutation in the LRRK2 Gene
AbstractThe search for new polymorphisms associated with hereditary diseases is important for diagnostics and the study of the disease’s development...
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In vitro genome editing rescues parkinsonism phenotypes in induced pluripotent stem cells-derived dopaminergic neurons carrying LRRK2 p.G2019S mutation
BackgroundThe c.G6055A (p.G2019S) mutation in leucine-rich repeat kinase 2 ( LRRK2 ) is the most prevalent genetic cause of Parkinson’s disease (PD)....
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Mitochondrial Drp1 recognizes and induces excessive mPTP opening after hypoxia through BAX-PiC and LRRK2-HK2
Mitochondrial mass imbalance is one of the key causes of cardiovascular dysfunction after hypoxia. The activation of dynamin-related protein 1...
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The parkinsonian LRRK2 R1441G mutation shows macroautophagy-mitophagy dysregulation concomitant with endoplasmic reticulum stress
Autophagy is a mechanism responsible for the degradation of cellular components to maintain their homeostasis. However, autophagy is commonly altered...
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Structure of LRRK1 and mechanisms of autoinhibition and activation
Leucine Rich Repeat Kinase 1 and 2 (LRRK1 and LRRK2) are homologs in the ROCO family of proteins in humans. Despite their shared domain architecture...
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Kinase inhibition of G2019S-LRRK2 enhances autolysosome formation and function to reduce endogenous alpha-synuclein intracellular inclusions
The Parkinson’s disease (PD)-associated kinase Leucine-Rich Repeat Kinase 2 (LRRK2) is a crucial modulator of the autophagy-lysosome pathway, but...
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The role of tyrosine hydroxylase–dopamine pathway in Parkinson’s disease pathogenesis
BackgroundParkinson’s disease (PD) is characterized by selective and progressive dopamine (DA) neuron loss in the substantia nigra and other brain...
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Multi-method computational evaluation of the inhibitors against leucine-rich repeat kinase 2 G2019S mutant for Parkinson's disease
Leucine-rich repeat kinase 2 G2019S mutant (LRRK2 G2019S) is a potential target for Parkinson's disease therapy. In this work, the computational...
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Iron-induced cytotoxicity mediated by endolysosomal TRPML1 channels is reverted by TFEB
Increased brain iron content has been consistently reported in sporadic Parkinson’s disease (PD) patients, and an increase in cytosolic free iron is...
