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Publication : The function of orthologues of the human Parkinson's disease gene LRRK2 across species: implications for disease modelling in preclinical research.

First Author  Langston RG Year  2016
Journal  Biochem J Volume  473
Issue  3 Pages  221-32
PubMed ID  26811536 Mgi Jnum  J:237645
Mgi Id  MGI:5816408 Doi  10.1042/BJ20150985
Citation  Langston RG, et al. (2016) The function of orthologues of the human Parkinson's disease gene LRRK2 across species: implications for disease modelling in preclinical research. Biochem J 473(3):221-32
abstractText  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.
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