Kinase activity of mutant LRRK2 mediates neuronal toxicity

By Wanli W. Smith, Z. Pei, Haibing Jiang, Valina L. Dawson, T. Dawson, Christopher A. Ross. Nature Neuroscience, 2006

669 citations recorded by the source corpus.

Subfields: Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/79f1bc9221d4fb2b7c1dc1323aa101e01f9b600a

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Neurology

1. H. Ko
2. Valina L. Dawson
3. T. Dawson
4. A. Lutz
5. Christian Haass
6. T. Palmer
7. K. Winklhofer
8. Nicole Exner

In Physiology

1. A. Lutz
2. Christian Haass
3. H. Ko
4. U. Pandey
5. Valina L. Dawson
6. T. Dawson
7. C. Nichols
8. K. Winklhofer

Citations in the corpus

• Dopamine release in the basal ganglia (2011, background): “Enhanced LRRK2 kinase activity after G2019S mutation correlates with neurotoxicity in vitro (Smith et al., 2006), whereas LRRK2 inhibition is protective in vivo (Lee et al., 2010).”
• Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequences (2012, positive): “Overexpression of pathogenic LRRK2 mutants in cultured cells, primary neurons or rodents causes cellular toxicity, which is dependent on the kinase activity (Greggio et al , 2006; Smith et al , 2006; West et al , 2007; Ho et al , 2009; Dusonchet et al , 2011).”
• Human Disease Models in Drosophila melanogaster and the Role of the Fly in Therapeutic Drug Discovery (2011, background): “It has been shown that the disease-associated mutations of LRRK2 can increase its kinase activity and thereby its toxicity (Smith et al., 2006; West et al., 2007).”
• Genetic Animal Models of Parkinson’s Disease (2010, positive): “In cellular models, overexpression of disease-causing mutations of LRRK2 are toxic, and the toxicity is kinase and GTP-binding dependent (Greggio et al., 2006; Smith et al., 2006; West et al., 2007b).”
• LRRK2 Mutant iPSC-Derived DA Neurons Demonstrate Increased Susceptibility to Oxidative Stress (2011, positive): “Studies from animal and cellular models have shown that certain mutations in the LRRK2 gene locus can increase its kinase activity, which contributes to neurotoxicity, possibly via oxidative stress pathways (Heo et al., 2010; MacLeod et al., 2006; Smith et al., 2006; West et al., 2005).”
• Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity. (2007, background): “Besides large in vitro assays that biochemically characterize LRRK2 protein, a number of previous studies have applied exogenous LRRK2 expression to various cell systems (17,18).”