LRRK2 mouse models: Dissecting the behavior, striatal neurochemistry and neurophysiology of PD pathogenesis

Mattia Volta, Heather L Melrose

Research output: Contribution to journalReview article

10 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)113-122
Number of pages10
JournalBiochemical Society Transactions
Volume45
Issue number1
DOIs
StatePublished - Feb 8 2017

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Neurophysiology
Neurochemistry
Corpus Striatum
Leucine
Parkinson Disease
Phosphotransferases
Dopamine
Animal Behavior
Animals
Neuronal Plasticity
Aptitude
Genetic Models
Animal Models
Plasticity
Phenotype
Mutation
Therapeutics
Research
Pharmaceutical Preparations
Mouse Lrrk2 protein

ASJC Scopus subject areas

  • Biochemistry

Cite this

LRRK2 mouse models : Dissecting the behavior, striatal neurochemistry and neurophysiology of PD pathogenesis. / Volta, Mattia; Melrose, Heather L.

In: Biochemical Society Transactions, Vol. 45, No. 1, 08.02.2017, p. 113-122.

Research output: Contribution to journalReview article

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