title: The function of orthologues of the human Parkinson's disease gene LRRK2 across species: implications for disease modelling in preclinical research.
abstract: In the period since LRRK2 (leucine-rich repeat kinase 2) was identified as a causal gene for late-onset autosomal dominant parkinsonism, a great deal of work has been aimed at understanding whether the LRRK2 protein might be a druggable target for Parkinson's disease (PD). As part of this effort, animal models have been developed to explore both the normal and the pathophysiological roles of LRRK2. However, LRRK2 is part of a wider family of proteins whose functions in different organisms remain poorly understood. In this review, we compare the information available on biochemical properties of LRRK2 homologues and orthologues from different species from invertebrates (e.g. Caenorhabditis elegans and Drosophila melanogaster) to mammals. We particularly discuss the mammalian LRRK2 homologue, LRRK1, and those species where there is only a single LRRK homologue, discussing examples where each of the LRRK family of proteins has distinct properties as well as those cases where there appear to be functional redundancy. We conclude that uncovering the function of LRRK2 orthologues will help to elucidate the key properties of human LRRK2 as well as to improve understanding of the suitability of different animal models for investigation of LRRK2-related PD.
authors.affiliation: Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, NIA, NIH, Bethesda, MD 20892, U.S.A.
authors.forename: Rebekah G
authors.initials: RG
authors.lastname: Langston
authors.affiliation: Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, NIA, NIH, Bethesda, MD 20892, U.S.A.
authors.forename: Iakov N
authors.initials: IN
authors.lastname: Rudenko
authors.affiliation: Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, NIA, NIH, Bethesda, MD 20892, U.S.A. cookson@mail.nih.gov.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Cookson
mesh_terms: D000818:Animals; D035843:Biomedical Research; D017173:Caenorhabditis elegans; D004195:Disease Models, Animal; D004331:Drosophila melanogaster; D006801:Humans; D010300:Parkinson Disease / Q000201:enzymology* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D017346:Protein Serine-Threonine Kinases
keywords: GTPase; LRRK2 homologue; animal models; dopaminergic neurons; kinase; neurodegeneration; preclinical research
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