Progress in LRRK2-Associated Parkinson's Disease Animal Models

doi:10.3389/fnins.2020.00674

Review

. 2020 Jul 15:14:674.

doi: 10.3389/fnins.2020.00674. eCollection 2020.

Progress in LRRK2-Associated Parkinson's Disease Animal Models

Steven P Seegobin^{1

2

3}, George R Heaton^{1

2

3}, Dongxiao Liang^{1

2

3

4}, Insup Choi^{1

2

3}, Marian Blanca Ramirez^{1

2

3}, Beisha Tang^{4

5}, Zhenyu Yue^{1

2

3}

Affiliations

¹ Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
² Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
³ Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
⁴ Department of Neurology, Xiangya Hospital, Central South University, Hunan, China.
⁵ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Hunan, China.

PMID: 32765209
PMCID: PMC7381130
DOI: 10.3389/fnins.2020.00674

Review

Progress in LRRK2-Associated Parkinson's Disease Animal Models

Steven P Seegobin et al. Front Neurosci. 2020.

. 2020 Jul 15:14:674.

doi: 10.3389/fnins.2020.00674. eCollection 2020.

Authors

Steven P Seegobin^{1

2

3}, George R Heaton^{1

2

3}, Dongxiao Liang^{1

2

3

4}, Insup Choi^{1

2

3}, Marian Blanca Ramirez^{1

2

3}, Beisha Tang^{4

5}, Zhenyu Yue^{1

2

3}

Affiliations

¹ Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
² Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
³ Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
⁴ Department of Neurology, Xiangya Hospital, Central South University, Hunan, China.
⁵ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Hunan, China.

PMID: 32765209
PMCID: PMC7381130
DOI: 10.3389/fnins.2020.00674

Abstract

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent cause of familial Parkinson's disease (PD). Several genetic manipulations of the LRRK2 gene have been developed in animal models such as rodents, Drosophila, Caenorhabditis elegans, and zebrafish. These models can help us further understand the biological function and derive potential pathological mechanisms for LRRK2. Here we discuss common phenotypic themes found in LRRK2-associated PD animal models, highlight several issues that should be addressed in future models, and discuss emerging areas to guide their future development.

Keywords: C. elegans; Drosophila; LRRK2; models; phenotypes; rodent; zebrafish.

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References

1. Adams J. R., Van Netten H., Schulzer M., Mak E., Mckenzie J., Strongosky A., et al. (2005). PET in LRRK2 mutations: comparison to sporadic Parkinson’s disease and evidence for presymptomatic compensation. Brain 128 2777–2785. 10.1093/brain/awh607 - DOI - PubMed
1. Andres-Mateos E., Mejias R., Sasaki M., Li X., Lin B. M., Biskup S., et al. (2009). Unexpected lack of hypersensitivity in LRRK2 knock-out mice to MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). J. Neurosci. 29 15846–15850. 10.1523/JNEUROSCI.4357-09.2009 - DOI - PMC - PubMed
1. Arbez N., He X., Huang Y., Ren M., Liang Y., Nucifora F., et al. (2019). G2019S-LRRK2 mutation enhances MPTP-linked parkinsonism in mice. Hum. Molec. Genet. 29 580–590. 10.1093/hmg/ddz271 - DOI - PMC - PubMed
1. Arranz A. M., Delbroek L., Kolen K., Van Guimara M. R., Daneels G., Matta S., et al. (2015). LRRK2 functions in synaptic vesicle endocytosis through a kinase- dependent mechanism. J. Cell. Sci. 128 541–552. 10.1242/jcs.158196 - DOI - PubMed
1. Bae E. J., Kim D. K., Kim C., Mante M., Adame A., Rockenstein E., et al. (2018). LRRK2 kinase regulates α-synuclein propagation via RAB35 phosphorylation. Nat. Commun. 9:18. 10.1038/s41467-018-05958-z - DOI - PMC - PubMed

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[1] Adams J. R., Van Netten H., Schulzer M., Mak E., Mckenzie J., Strongosky A., et al. (2005). PET in LRRK2 mutations: comparison to sporadic Parkinson’s disease and evidence for presymptomatic compensation. Brain 128 2777–2785. 10.1093/brain/awh607 - DOI - PubMed

[2] Adams J. R., Van Netten H., Schulzer M., Mak E., Mckenzie J., Strongosky A., et al. (2005). PET in LRRK2 mutations: comparison to sporadic Parkinson’s disease and evidence for presymptomatic compensation. Brain 128 2777–2785. 10.1093/brain/awh607 - DOI - PubMed

[3] Andres-Mateos E., Mejias R., Sasaki M., Li X., Lin B. M., Biskup S., et al. (2009). Unexpected lack of hypersensitivity in LRRK2 knock-out mice to MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). J. Neurosci. 29 15846–15850. 10.1523/JNEUROSCI.4357-09.2009 - DOI - PMC - PubMed

[4] Andres-Mateos E., Mejias R., Sasaki M., Li X., Lin B. M., Biskup S., et al. (2009). Unexpected lack of hypersensitivity in LRRK2 knock-out mice to MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). J. Neurosci. 29 15846–15850. 10.1523/JNEUROSCI.4357-09.2009 - DOI - PMC - PubMed

[5] Arbez N., He X., Huang Y., Ren M., Liang Y., Nucifora F., et al. (2019). G2019S-LRRK2 mutation enhances MPTP-linked parkinsonism in mice. Hum. Molec. Genet. 29 580–590. 10.1093/hmg/ddz271 - DOI - PMC - PubMed

[6] Arbez N., He X., Huang Y., Ren M., Liang Y., Nucifora F., et al. (2019). G2019S-LRRK2 mutation enhances MPTP-linked parkinsonism in mice. Hum. Molec. Genet. 29 580–590. 10.1093/hmg/ddz271 - DOI - PMC - PubMed

[7] Arranz A. M., Delbroek L., Kolen K., Van Guimara M. R., Daneels G., Matta S., et al. (2015). LRRK2 functions in synaptic vesicle endocytosis through a kinase- dependent mechanism. J. Cell. Sci. 128 541–552. 10.1242/jcs.158196 - DOI - PubMed

[8] Arranz A. M., Delbroek L., Kolen K., Van Guimara M. R., Daneels G., Matta S., et al. (2015). LRRK2 functions in synaptic vesicle endocytosis through a kinase- dependent mechanism. J. Cell. Sci. 128 541–552. 10.1242/jcs.158196 - DOI - PubMed

[9] Bae E. J., Kim D. K., Kim C., Mante M., Adame A., Rockenstein E., et al. (2018). LRRK2 kinase regulates α-synuclein propagation via RAB35 phosphorylation. Nat. Commun. 9:18. 10.1038/s41467-018-05958-z - DOI - PMC - PubMed

[10] Bae E. J., Kim D. K., Kim C., Mante M., Adame A., Rockenstein E., et al. (2018). LRRK2 kinase regulates α-synuclein propagation via RAB35 phosphorylation. Nat. Commun. 9:18. 10.1038/s41467-018-05958-z - DOI - PMC - PubMed

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Progress in LRRK2-Associated Parkinson's Disease Animal Models

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Progress in LRRK2-Associated Parkinson's Disease Animal Models

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