The biology and pathology of the familial Parkinson's disease protein LRRK2
- PMID: 20187256
- DOI: 10.1002/mds.22717
The biology and pathology of the familial Parkinson's disease protein LRRK2
Abstract
Parkinson's disease (PD) is typically a sporadic illness, but the past decade has witnessed the identification of mutations responsible for multiple familial forms of the disease. The proposed functions of some of these genes (e.g., E3 ubiquitin ligase, redox-dependent chaperone) have led to the hypothesis that dysfunction of protein quality control pathways contributes to PD neurodegeneration. However, the key signaling events that act downstream of misfolded proteins to cause cell death remain poorly defined. The discovery of the familial PD kinase leucine-rich repeat kinase 2 (LRRK2) holds great promise for the elucidation of signaling events relevant to PD neurodegeneration. This review will summarize current knowledge of the clinical and cell biological features of LRRK2, the most common inherited cause of Parkinsonism.
Similar articles
-
LRRK2, a puzzling protein: insights into Parkinson's disease pathogenesis.Exp Neurol. 2014 Nov;261:206-16. doi: 10.1016/j.expneurol.2014.05.025. Epub 2014 Jun 4. Exp Neurol. 2014. PMID: 24907399 Free PMC article. Review.
-
Clinical genetics of Parkinson's disease and related disorders.Parkinsonism Relat Disord. 2007;13 Suppl 3:S229-32. doi: 10.1016/S1353-8020(08)70007-5. Parkinsonism Relat Disord. 2007. PMID: 18267241 Review.
-
The LRRK2 G2019S mutation as the cause of Parkinson's disease in Ashkenazi Jews.J Neural Transm (Vienna). 2009 Nov;116(11):1473-82. doi: 10.1007/s00702-009-0303-0. J Neural Transm (Vienna). 2009. PMID: 19756366 Review.
-
Leucine-Rich Repeat Kinase (LRRK2) Genetics and Parkinson's Disease.Adv Neurobiol. 2017;14:3-30. doi: 10.1007/978-3-319-49969-7_1. Adv Neurobiol. 2017. PMID: 28353276 Review.
-
The Cell Biology of LRRK2 in Parkinson's Disease.Mol Cell Biol. 2021 Apr 22;41(5):e00660-20. doi: 10.1128/MCB.00660-20. Print 2021 Apr 22. Mol Cell Biol. 2021. PMID: 33526455 Free PMC article. Review.
Cited by
-
Mechanisms of aging-related proteinopathies in Caenorhabditis elegans.Exp Mol Med. 2016 Oct 7;48(10):e263. doi: 10.1038/emm.2016.109. Exp Mol Med. 2016. PMID: 27713398 Free PMC article. Review.
-
Pathogenic LRRK2 requires secondary factors to induce cellular toxicity.Biosci Rep. 2020 Oct 30;40(10):BSR20202225. doi: 10.1042/BSR20202225. Biosci Rep. 2020. PMID: 32975566 Free PMC article.
-
Parkinson's disease dementia and potential therapeutic strategies.CNS Neurosci Ther. 2011 Feb;17(1):32-44. doi: 10.1111/j.1755-5949.2010.00216.x. Epub 2010 Dec 28. CNS Neurosci Ther. 2011. PMID: 21199444 Free PMC article. Review.
-
Distinctive roles of Rac1 and Rab29 in LRRK2 mediated membrane trafficking and neurite outgrowth.J Biomed Res. 2018 Mar 26;32(2):145-156. doi: 10.7555/JBR.31.20170039. J Biomed Res. 2018. PMID: 29336357 Free PMC article.
-
R1441C and G2019S LRRK2 knockin mice have distinct striatal molecular, physiological, and behavioral alterations.Commun Biol. 2022 Nov 10;5(1):1211. doi: 10.1038/s42003-022-04136-8. Commun Biol. 2022. PMID: 36357506 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous
