Multiplying messages LRRK beneath Parkinson disease.
Ann Arbor, United States. In Cell, May 2014
link PD protein leucine-rich repeat kinase 2 (LRRK2) to abnormalities of translational control, a pathogenic mechanism implicated in an increasing number of CNS neurodegenerative diseases, as well as in normal aging.
Interaction of LRRK2 with kinase and GTPase signaling cascades.
Boston, United States. In Front Mol Neurosci, Dec 2013
LRRK2 is a protein that interacts with a plethora of signaling molecules, but the complexity of LRRK2 function presents a challenge for understanding the role of LRRK2 in the pathophysiology of Parkinson's disease (PD).
Genetics and genomics of Parkinson's disease.
Vancouver, Canada. In Genome Med, Dec 2013
Recent discoveries in sporadic, Mendelian and more complex forms of parkinsonism provide novel insight into disease etiology; 28 genes, including those encoding alpha-synuclein (SNCA), leucine-rich repeat kinase 2 (LRRK2) and microtubule-associated protein tau (MAPT), have been linked and/or associated with PD.
Parkinson's disease-implicated kinases in the brain; insights into disease pathogenesis.
Australia. In Front Mol Neurosci, Dec 2013
Elevated phosphorylation of the PD-defining pathological protein, α-synuclein, correlates with its aggregation and toxic accumulation in neurons, whilst genetic missense mutations in the kinases PTEN-induced putative kinase 1 and leucine-rich repeat kinase 2, increase susceptibility to PD. Experimental evidence also links kinases of the phosphoinositide 3-kinase and mitogen-activated protein kinase signaling pathways, amongst others, to PD. Understanding how the levels or activities of these enzymes or their substrates change in brain tissue in relation to pathological states can provide insight into disease pathogenesis.
Progressive degeneration of human neural stem cells caused by pathogenic LRRK2.
Beijing, China. In Nature, 2012
We decided to evaluate nuclear organization in the context of ageing-associated disorders by focusing on a leucine-rich repeat kinase 2 (LRRK2) dominant mutation (G2019S; glycine-to-serine substitution at amino acid 2019), which is associated with familial and sporadic Parkinson's disease as well as impairment of adult neurogenesis in mice.
Pathological roles of α-synuclein in neurological disorders.
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Athens, Greece. In Lancet Neurol, 2011
α-Synuclein also seems to be linked to other genetic forms of Parkinson's disease, such as those linked to mutations in GBA or LRRK2, possibly through common effects on autophagy and lysosomal function.