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

The Biochemical Journal
Rebekah G LangstonMark R Cookson

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...Continue Reading

References

Mar 14, 2002·Annals of Neurology·Manabu FunayamaFumiya Obata
Dec 25, 2002·Neurobiology of Aging·Heiko BraakEva Braak
Dec 5, 2003·Biochimica Et Biophysica Acta·Leonard Bosgraaf, Peter J M Van Haastert
Aug 5, 2004·Annals of Neurology·Mirthe M PonsenHenk W Berendse
Nov 16, 2004·Neuron·Coro Paisán-RuízAndrew B Singleton
Oct 26, 2005·Cellular Signalling·Daniel KorrBertram Weiss
Dec 3, 2005·Human Molecular Genetics·Christian Johannes GloecknerMarius Ueffing
Feb 21, 2006·The European Journal of Neuroscience·Javier Simón-SánchezJordi Pérez-Tur
Mar 15, 2006·Annals of Neurology·Dagmar GalterLars Olson
Apr 18, 2006·Trends in Neurosciences·Ignacio F MataKathleen A Gallo
Jun 6, 2006·Neurobiology of Disease·Elisa GreggioMark R Cookson
Jun 15, 2006·Journal of Neurochemistry·Jean-Marc TaymansVeerle Baekelandt
Sep 13, 2006·Molecular Biology and Evolution·Ignacio Marín
Nov 23, 2006·Annals of Neurology·Saskia BiskupValina L Dawson
Feb 28, 2007·Neuroscience Letters·Kristoffer HaugarvollMatthew J Farrer
Mar 10, 2007·Current Biology : CB·Aisa Sakaguchi-NakashimaNaoki Hisamoto
May 15, 2007·Biochemical and Biophysical Research Communications·Sung Bae LeeJongkyeong Chung
Nov 30, 2007·BMC Neuroscience·Saskia BiskupAndrew B West
Feb 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Zhaohui LiuWanli W Smith
Mar 7, 2008·Neuro-degenerative Diseases·Benjamin WolozinMisha Riley
May 1, 2008·Experimental Cell Research·Narae ShinWongi Seol
Jun 5, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ignacio MarínPeter J M van Haastert
Jun 5, 2008·Journal of Molecular Evolution·Ignacio Marín
Jun 10, 2008·Lancet Neurology·Daniel G HealyUNKNOWN International LRRK2 Consortium
Mar 3, 2009·The Journal of Biological Chemistry·Julia SämannEnrico Schmidt
Jul 25, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Shamol SahaBenjamin Wolozin
Aug 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Youren TongJie Shen
Aug 29, 2009·Journal of Neurochemistry·Christian L KleinPhilipp J Kahle
Sep 11, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Chee-Hoe NgKah-Leong Lim
Nov 17, 2009·Nature Genetics·Javier Simón-SánchezThomas Gasser
Dec 18, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Eva Andres-MateosValina L Dawson
Dec 31, 2009·PloS One·Nathan D JorgensenWilliam T Dauer

❮ Previous
Next ❯

Citations

Jul 17, 2016·Proceedings of the National Academy of Sciences of the United States of America·Mark R Cookson
Jan 18, 2018·International Journal of Molecular Sciences·Joon W Shim, Joseph R Madsen
Feb 7, 2018·Stem Cells and Development·Scott C Vermilyea, Marina E Emborg
Jul 6, 2020·Journal of Neuroscience Research·Jinelle M Wint, Howard I Sirotkin
Sep 15, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Prasannakumar DeshpandeEleanor T Coffey
Aug 29, 2018·Nature Communications·Eun-Jin BaeSeung-Jae Lee
Aug 9, 2020·Frontiers in Neuroscience·Steven P SeegobinZhenyu Yue
May 26, 2018·Brain : a Journal of Neurology·Elena KozinaRichard J Smeyne
Aug 1, 2020·Seminars in Cell & Developmental Biology·Gregory D Cuny, Alexei Degterev
Feb 3, 2021·Molecular and Cellular Biology·Ahsan UsmaniAnnie Hiniker
Aug 24, 2021·Frontiers in Aging Neuroscience·Maria Shadrina, Petr Slominsky

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

© 2021 Meta ULC. All rights reserved