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Mechanisms of LRRK2-Mediated Neurodegeneration

  • Genetics (V Bonifati, Section Editor)
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Abstract

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene represent the most common cause of familial Parkinson’s disease (PD), whereas common variation at the LRRK2 locus is associated with an increased risk of idiopathic PD. Considerable progress has been made toward understanding the biological functions of LRRK2 and the molecular mechanisms underlying the pathogenic effects of disease-associated mutations. The development of neuronal culture models and transgenic or viral-based rodent models have proved useful for identifying a number of emerging pathways implicated in LRRK2-dependent neuronal damage, including the microtubule network, actin cytoskeleton, autophagy, mitochondria, vesicular trafficking, and protein quality control. However, many important questions remain to be posed and answered. Elucidating the molecular mechanisms and pathways underlying LRRK2-mediated neurodegeneration is critical for the identification of new molecular targets for therapeutic intervention in PD. In this review we discuss recent advances and unanswered questions in understanding the pathophysiology of LRRK2.

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Acknowledgments

The authors are grateful for funding support from the Swiss National Science Foundation (grant no. 310030_127478), Michael J. Fox Foundation for Parkinson’s Research, Parkinson Schweiz, NIH, NINDS (NS076160), EPFL, and Merck-Serono AG.

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  1. Laboratory of Molecular Neurodegenerative Research, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), SV-BMI-LMNR, AI 2150, Station 15, 1015, Lausanne, Switzerland

    Elpida Tsika & Darren J. Moore

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Tsika, E., Moore, D.J. Mechanisms of LRRK2-Mediated Neurodegeneration. Curr Neurol Neurosci Rep 12, 251–260 (2012). https://doi.org/10.1007/s11910-012-0265-8

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