Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of familial Parkinson's disease (PD), resembling the sporadic disorder. Intensive effort has been directed toward LRRK2 mouse modeling and investigation, aimed at reproducing the human disease to inform mechanistic studies of pathogenesis and design of neuroprotective therapies. The physiological function of LRRK2 is still under exploration, but a clear role in striatal neurophysiology and animal behavior has emerged. Alterations in LRRK2 impair dopamine (DA) transmission, regulation and signaling, in addition to corticostriatal synaptic plasticity. Consistently, several subtle abnormalities in motor and nonmotor abilities have been demonstrated in LRRK2 genetic mouse models, generally paralleling preclinical symptoms of early DA dysfunction. However, the variability in model design and phenotypes observed requires a critical approach in interpreting the results, adapting the model used to the specific research question. Etiologically appropriate knockin mice might represent the ultimate animal model in which to study early disease mechanisms and therapies as well as to investigate drug effectiveness and off-target consequences.
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February 2017
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The surface of the catalytic subunit of protein phosphatase PP1 (central 3D-structure) has many binding sites for regulatory proteins that are embedded in regulatory networks (coloured circles linked by lines). Please see pp. 89–99 for more information. Image provided by Mathieu Bollen.
Review Article|
February 15 2017
LRRK2 mouse models: dissecting the behavior, striatal neurochemistry and neurophysiology of PD pathogenesis
Mattia Volta;
1Center for Biomedicine, EURAC Research, Via Galvani 31, Bolzano 39100, Italy
Correspondence: Mattia Volta (mattia.volta@eurac.edu) or Heather Melrose (melrose.heather@mayo.edu)
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Heather Melrose
2Department of Neuroscience, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, U.S.A.
Correspondence: Mattia Volta (mattia.volta@eurac.edu) or Heather Melrose (melrose.heather@mayo.edu)
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Publisher: Portland Press Ltd
Received:
August 10 2016
Revision Received:
October 21 2016
Accepted:
October 25 2016
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society
2017
Biochem Soc Trans (2017) 45 (1): 113–122.
Article history
Received:
August 10 2016
Revision Received:
October 21 2016
Accepted:
October 25 2016
Citation
Mattia Volta, Heather Melrose; LRRK2 mouse models: dissecting the behavior, striatal neurochemistry and neurophysiology of PD pathogenesis. Biochem Soc Trans 8 February 2017; 45 (1): 113–122. doi: https://doi.org/10.1042/BST20160238
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