Models of LRRK2-Associated Parkinson's Disease

Yulan Xiong; Ted M Dawson; Valina L Dawson

doi:10.1007/978-3-319-49969-7_9

Models of LRRK2-Associated Parkinson's Disease

Adv Neurobiol. 2017:14:163-191. doi: 10.1007/978-3-319-49969-7_9.

Authors

Yulan Xiong^{1

2

3}, Ted M Dawson^{4

5

6

7

8}, Valina L Dawson^{9

10

11

12

13}

Affiliations

¹ Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. yulanxiong@ksu.edu.
² Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. yulanxiong@ksu.edu.
³ Department of Anatomy and Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS, 66506, USA. yulanxiong@ksu.edu.
⁴ Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. vdawson@jhmi.edu.
⁵ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. vdawson@jhmi.edu.
⁶ Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. vdawson@jhmi.edu.
⁷ Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. vdawson@jhmi.edu.
⁸ Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA, 70130-2685, USA. vdawson@jhmi.edu.
⁹ Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. tdawson@jhmi.edu.
¹⁰ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. tdawson@jhmi.edu.
¹¹ Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. tdawson@jhmi.edu.
¹² Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA, 70130-2685, USA. tdawson@jhmi.edu.
¹³ Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. tdawson@jhmi.edu.

Abstract

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic causes of Parkinson's disease (PD) and also one of the strongest genetic risk factors in sporadic PD. The LRRK2 protein contains a GTPase and a kinase domain and several protein-protein interaction domains. Both in vitro and in vivo assays in different model systems have provided tremendous insights into the molecular mechanisms underlying LRRK2-induced dopaminergic neurodegeneration. Among all the model systems, animal models are crucial tools to study the pathogenesis of human disease. How do the animal models recapitulate LRRK2-induced dopaminergic neuronal loss in human PD? To answer this question, this review focuses on the discussion of the animal models of LRRK2-associated PD including genetic- and viral-based models.

Keywords: Animal models; LRRK2; Parkinson’s disease.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Disease Models, Animal*
Humans
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics*
Mutation
Parkinson Disease / genetics*

Substances

Leucine-Rich Repeat Serine-Threonine Protein Kinase-2

Abstract

Publication types

MeSH terms

Substances

Grants and funding