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LRRK2 signaling pathways: the key to unlocking neurodegeneration?

Berwick, DC; Harvey, K; (2011) LRRK2 signaling pathways: the key to unlocking neurodegeneration? Trends Cell Biol , 21 (5) pp. 257-265. 10.1016/j.tcb.2011.01.001.

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Mutations in PARK8, encoding leucine-rich repeat kinase 2 (LRRK2), are a major cause of Parkinson's disease. We contrast data suggesting that changes in LRRK2 activity cause alterations in mitogen-activated protein kinase, translational control, tumor necrosis factor α/Fas ligand and Wnt signaling pathways with the cell biological functions of LRRK2 such as vesicle trafficking. Despite scarce in vivo data on cell signaling, involvement in diverse cell biological functions suggests a role for LRRK2 as an upstream regulator in events leading to neurodegeneration. To stimulate discussion and give direction for future research, we further suggest that despite the importance of the catalytic activity for cytotoxicity, the main cellular function of LRRK2 is linked to assembly of signaling complexes.

Type: Article
Title: LRRK2 signaling pathways: the key to unlocking neurodegeneration?
Location: England
DOI: 10.1016/j.tcb.2011.01.001
Keywords: Animals, Humans, Intracellular Signaling Peptides and Proteins, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Mutation, Parkinson Disease, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Signal Transduction, Tumor Necrosis Factors, Wnt Proteins
URI: http://discovery.ucl.ac.uk/id/eprint/1350598
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