Article

Pathogenic mutations in LRRK2 sequester Rab8a to damaged lysosomes and regulate transferrin-mediated iron uptake in microglia

2020-07-27

Abstract excerpt

Mutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal dominant Parkinson’s disease (PD) while polymorphic LRRK2 variants are associated with sporadic PD. PD-linked mutations increase LRRK2 kinase activity and induce neurotoxicity in vitro and in vivo . The small GTPase Rab8a is a LRRK2 kinase substrate and is involved in receptor-mediated recycling and endocytic trafficking of transferrin, but the ef...

Topics

Open a Topic to create a Post that cites this publication.

Identifiers and source

Literature Corpus work: f0cac2f2-12c3-5bec-9abe-e56424412215
DOI: 10.1101/2020.07.27.219501

Open publication

Related research

Semantic proximity does not establish scientific evidence.

Click a neighbor to travelStep 1 · 12 closest

Pathogenic mutations in LRRK2 sequester Rab8a to damaged lysosomes and regulate transferrin-mediated iron uptake in microgliaDOI 10.1101/2020.07.27.219501Read

Mutations in LRRK2 linked to Parkinson disease sequester Rab8a to damaged lysosomes and regulate transferrin-mediated iron uptake in microglia.Semantic proximity Read

An LRRK2 variant blocks NCOA4 trafficking upon iron overload, leading to ferroptotic death.Semantic proximity Read

LRRK2 mutations block NCOA4 trafficking upon iron overload leading to ferroptotic deathSemantic proximity Read

Parkinson’s disease LRRK2 mutations dysregulate iron homeostasis and promote oxidative stress and ferroptosis in human neurons and astrocytesSemantic proximity Read

A LRRK2/dLRRK-mediated lysosomal pathway that contributes to glial cell death and DA neuron survivalSemantic proximity Read

LRRK2 kinase dependent and independent function on endolysosomal repair promotes macrophage cell deathSemantic proximity Read

LRRK2 mutations: at the crossroads of dopamine, iron, and calcium imbalance in Parkinson's disease.Semantic proximity Read

A LRRK2/dLRRK-mediated lysosomal pathway that contributes to glial cell death and DA neuron survival.Semantic proximity Read

Pathogenic LRRK2 mutations, through increased kinase activity, produce enlarged lysosomes with reduced degradative capacity and increase ATP13A2 expression.Semantic proximity Read

LRRK2 Is Recruited to Phagosomes and Co-recruits RAB8 and RAB10 in Human Pluripotent Stem Cell-Derived MacrophagesSemantic proximity Read

LRRK2 is recruited to phagosomes and co-recruits Rab8 and Rab10 in human pluripotent stem cell-derived macrophagesSemantic proximity Read

Vps35 p. D620N causes Lrrk2 kinase hyperactivity, chronic microglial activation and inflammationSemantic proximity Read