Jillian H. Kluss
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View article: A Common PD-Risk <i>GBA1</i> Variant Disrupts LIMP2 Interaction, Impairs Glucocerebrosidase Function, and Drives Lysosomal and Mitochondrial Dysfunction
A Common PD-Risk <i>GBA1</i> Variant Disrupts LIMP2 Interaction, Impairs Glucocerebrosidase Function, and Drives Lysosomal and Mitochondrial Dysfunction Open
Summary Variants in GBA1 cause Gaucher disease (GD), a lysosomal storage disorder, and represent the most common genetic risk factor for Parkinson’s disease (PD). While some GBA1 variants are associated with both GD and PD, several coding …
View article: JIP4 and RILPL1 utilize opposing motor force to dynamically regulate lysosomal tubulation
JIP4 and RILPL1 utilize opposing motor force to dynamically regulate lysosomal tubulation Open
Lysosomes are dynamic organelles that remodel their membrane in response to stimuli. We previously uncovered a process we term LYsosomal Tubulation/sorting driven by LRRK2 (LYTL), wherein damaged lysosomes generate tubules sorted into vesi…
View article: Regulation of LRRK2 activity by metabolic stress and heavy metal exposure
Regulation of LRRK2 activity by metabolic stress and heavy metal exposure Open
Genetic variability in the gene encoding leucine-rich repeat kinase 2 (LRRK2) is associated with both familial and sporadic Parkinson's disease (PD). While LRRK2 is known to modulate vesicular trafficking and stress signaling through its p…
View article: Macrophage LRRK2 hyperactivity impairs autophagy and induces Paneth cell dysfunction
Macrophage LRRK2 hyperactivity impairs autophagy and induces Paneth cell dysfunction Open
LRRK2 polymorphisms (G2019S/N2081D) that increase susceptibility to Parkinson’s disease and Crohn’s disease (CD) lead to LRRK2 kinase hyperactivity and suppress autophagy. This connection suggests that LRRK2 kinase inhibition, a therapeuti…
View article: Mechanisms of lysosomal tubulation and sorting driven by LRRK2
Mechanisms of lysosomal tubulation and sorting driven by LRRK2 Open
Lysosomes are dynamic cellular structures that adaptively remodel their membrane in response to stimuli, including membrane damage. Lysosomal dysfunction plays a central role in the pathobiology of Parkinson's disease (PD). Gain-of-functio…
View article: Opposing actions of JIP4 and RILPL1 provide antagonistic motor force to dynamically regulate membrane reformation during lysosomal tubulation/sorting driven by LRRK2
Opposing actions of JIP4 and RILPL1 provide antagonistic motor force to dynamically regulate membrane reformation during lysosomal tubulation/sorting driven by LRRK2 Open
Lysosomes are dynamic cellular structures that adaptively remodel their membrane in response to stimuli, including membrane damage. We previously uncovered a process we term LYTL (LYsosomal Tubulation/sorting driven by Leucine-Rich Repeat …
View article: Identification of genetic risk loci and causal insights associated with Parkinson's disease in African and African admixed populations: a genome-wide association study
Identification of genetic risk loci and causal insights associated with Parkinson's disease in African and African admixed populations: a genome-wide association study Open
View article: Structure and regulation of full-length human leucine-rich repeat kinase 1
Structure and regulation of full-length human leucine-rich repeat kinase 1 Open
View article: Genome-wide Association Identifies Novel Etiological Insights Associated with Parkinson’s Disease in African and African Admixed Populations
Genome-wide Association Identifies Novel Etiological Insights Associated with Parkinson’s Disease in African and African Admixed Populations Open
Summary Background Understanding the genetic mechanisms underlying diseases in ancestrally diverse populations is a critical step towards the realization of the global application of precision medicine. The African and African admixed popu…
View article: Lysosomal positioning regulates Rab10 phosphorylation at LRRK2 <sup>+</sup> lysosomes
Lysosomal positioning regulates Rab10 phosphorylation at LRRK2 <sup>+</sup> lysosomes Open
Genetic variation at the leucine-rich repeat kinase 2 ( LRRK2 ) locus contributes to an enhanced risk of familial and sporadic Parkinson’s disease. Previous data have demonstrated that recruitment to various membranes of the endolysosomal …
View article: Leucine-rich repeat kinase 2 (LRRK2): an update on the potential therapeutic target for Parkinson’s disease
Leucine-rich repeat kinase 2 (LRRK2): an update on the potential therapeutic target for Parkinson’s disease Open
The growth of both target discovery and innovative drug design has sparked a lot of excitement for the future of how we treat Parkinson's disease. Given the immense focus on LRRK2 as a therapeutic target, it is expected within the next dec…
View article: Evaluation of Current Methods to Detect Cellular Leucine-Rich Repeat Kinase 2 (LRRK2) Kinase Activity
Evaluation of Current Methods to Detect Cellular Leucine-Rich Repeat Kinase 2 (LRRK2) Kinase Activity Open
Background: Coding variation in the Leucine rich repeat kinase 2 gene linked to Parkinson’s disease (PD) promotes enhanced activity of the encoded LRRK2 kinase, particularly with respect to autophosphorylation at S1292 and/or phosphorylati…
View article: Directing LRRK2 to membranes of the endolysosomal pathway triggers RAB phosphorylation and JIP4 recruitment
Directing LRRK2 to membranes of the endolysosomal pathway triggers RAB phosphorylation and JIP4 recruitment Open
Coding mutations in the Leucine-rich repeat kinase 2 (LRRK2) gene, which are associated with dominantly inherited Parkinson's disease (PD), lead to an increased activity of the encoded LRRK2 protein kinase. As such, kinase inhibitors are b…
View article: Mutations in LRRK2 linked to Parkinson disease sequester Rab8a to damaged lysosomes and regulate transferrin-mediated iron uptake in microglia
Mutations in LRRK2 linked to Parkinson disease sequester Rab8a to damaged lysosomes and regulate transferrin-mediated iron uptake in microglia Open
Mutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal dominant Parkinson disease (PD), while polymorphic LRRK2 variants are associated with sporadic PD. PD-linked mutations increase LRRK2 kinase activity and induce neurotoxicit…
View article: Preclinical modeling of chronic inhibition of the Parkinson’s disease associated kinase LRRK2 reveals altered function of the endolysosomal system in vivo
Preclinical modeling of chronic inhibition of the Parkinson’s disease associated kinase LRRK2 reveals altered function of the endolysosomal system in vivo Open
View article: Additional file 4 of Preclinical modeling of chronic inhibition of the Parkinson’s disease associated kinase LRRK2 reveals altered function of the endolysosomal system in vivo
Additional file 4 of Preclinical modeling of chronic inhibition of the Parkinson’s disease associated kinase LRRK2 reveals altered function of the endolysosomal system in vivo Open
Additional file 4:.
View article: Lysosomal positioning regulates Rab10 phosphorylation at LRRK2-positive lysosomes
Lysosomal positioning regulates Rab10 phosphorylation at LRRK2-positive lysosomes Open
Genetic variation at the Leucine-rich repeat kinase 2 (LRRK2) locus contributes to enhanced lifetime risk of familial and sporadic Parkinson’s disease. Previous data have demonstrated that recruitment to various membranes of the endolysoso…
View article: LRRK2 mediates tubulation and vesicle sorting from lysosomes
LRRK2 mediates tubulation and vesicle sorting from lysosomes Open
The Parkinson disease kinase LRRK2 translocates to the lysosomal membrane triggering lysosomal sorting through JIP4.
View article: Divergent Effects of G2019S and R1441C LRRK2 Mutations on LRRK2 and Rab10 Phosphorylations in Mouse Tissues
Divergent Effects of G2019S and R1441C LRRK2 Mutations on LRRK2 and Rab10 Phosphorylations in Mouse Tissues Open
Mutations in LRRK2 cause familial Parkinson’s disease and common variants increase disease risk. LRRK2 kinase activity and cellular localization are tightly regulated by phosphorylation of key residues, primarily Ser1292 and Ser935, which …
View article: Preclinical Modeling of Chronic Inhibition of the Parkinson’s Disease Associated Kinase LRRK2 Reveals Altered Function of the Endolysosomal System in Vivo
Preclinical Modeling of Chronic Inhibition of the Parkinson’s Disease Associated Kinase LRRK2 Reveals Altered Function of the Endolysosomal System in Vivo Open
BackgroundThe most common mutation in the Leucine-rich repeat kinase 2 gene (LRRK2), G2019S, causes familial Parkinson’s Disease (PD) and renders the encoded protein kinase hyperactive. To date, the molecular effects of chronic LRRK2 inhib…
View article: The Parkinson's Disease <scp>Genome‐Wide</scp> Association Study Locus Browser
The Parkinson's Disease <span>Genome‐Wide</span> Association Study Locus Browser Open
Background Parkinson's disease (PD) is a neurodegenerative disease with an often complex component identifiable by genome‐wide association studies. The most recent large‐scale PD genome‐wide association studies have identified more than 90…
View article: The Parkinson’s Disease GWAS Locus Browser
The Parkinson’s Disease GWAS Locus Browser Open
Parkinson’s disease (PD) is a neurodegenerative disease with an often complex genetic component identifiable by genome-wide association studies (GWAS). The most recent large scale PD GWASes have identified more than 90 independent risk var…
View article: In Vitro CRISPR/Cas9-Directed Gene Editing to Model LRRK2 G2019S Parkinson’s Disease in Common Marmosets
In Vitro CRISPR/Cas9-Directed Gene Editing to Model LRRK2 G2019S Parkinson’s Disease in Common Marmosets Open
Leucine-rich repeat kinase 2 (LRRK2) G2019S is a relatively common mutation, associated with 1–3% of Parkinson’s disease (PD) cases worldwide. G2019S is hypothesized to increase LRRK2 kinase activity. Dopaminergic neurons derived from indu…
View article: LRRK2 mediates tubulation and vesicle sorting from membrane damaged lysosomes
LRRK2 mediates tubulation and vesicle sorting from membrane damaged lysosomes Open
Mutations in the leucine rich repeat kinase 2 ( LRRK2 ) gene are a cause of familial and sporadic Parkinson’s disease (PD). Nonetheless, the biological functions of LRRK2 remain incompletely understood. Here, we observed that LRRK2 is recr…
View article: Mutations in Auxilin cause parkinsonism via impaired clathrin-mediated trafficking at the Golgi apparatus and synapse
Mutations in Auxilin cause parkinsonism via impaired clathrin-mediated trafficking at the Golgi apparatus and synapse Open
Parkinson’s disease (PD) is a common neurodegenerative motor disorder characterized in part by neuropathological lesions in the nigrostriatal pathway. Loss of function mutations in Auxilin, the major neuronal clathrin uncoating protein, ca…
View article: LRRK2 links genetic and sporadic Parkinson's disease
LRRK2 links genetic and sporadic Parkinson's disease Open
The past two decades in research has revealed the importance of leucine-rich repeat kinase 2 (LRRK2) in both monogenic and sporadic forms of Parkinson's disease (PD). In families, mutations in LRRK2 can cause PD with age-dependent but vari…
View article: Detection of endogenous S1292 LRRK2 autophosphorylation in mouse tissue as a readout for kinase activity
Detection of endogenous S1292 LRRK2 autophosphorylation in mouse tissue as a readout for kinase activity Open
Parkinson’s disease-linked mutations in LRRK2 enhance the kinase activity of the protein, therefore targeting LRRK2 kinase activity is a promising therapeutic approach. Phosphorylation at S935 of LRRK2 and of its Rab GTPase substrates have…
View article: LRRK2 G2019S-induced mitochondrial DNA damage is LRRK2 kinase dependent and inhibition restores mtDNA integrity in Parkinson’s disease
LRRK2 G2019S-induced mitochondrial DNA damage is LRRK2 kinase dependent and inhibition restores mtDNA integrity in Parkinson’s disease Open
Mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with increased risk for developing Parkinson's disease (PD). Previously, we found that LRRK2 G2019S mutation carriers have increased mitochondrial DNA (mtDNA) damage and afte…