All Outputs (33)

LRRK2 kinase activity is necessary for development and regeneration in Nematostella vectensis (2024)
Journal Article
Holmes, G., Ferguson, S., Lewis, P., & Echeverri, K. (2024). LRRK2 kinase activity is necessary for development and regeneration in Nematostella vectensis. Neural Development, 19(1), https://doi.org/10.1186/s13064-024-00193-3

Background The starlet sea anemone, Nematostella vectensis, is an emerging model organism with a high regenerative capacity, which was recently found to possess an orthologue to the human Leucine Rich Repeat Kinase 2 (LRRK2) gene. Mutations in this g... Read More about LRRK2 kinase activity is necessary for development and regeneration in Nematostella vectensis.

Common genetic risk for Parkinson's disease and dysfunction of the endo-lysosomal system (2024)
Journal Article
Bhore, N., Bogacki, E., OCallaghan, B., Plun-Favreau, H., Lewis, P., & Herbst, S. (2024). Common genetic risk for Parkinson's disease and dysfunction of the endo-lysosomal system. Philosophical Transactions of the Royal Society B: Biological Sciences, 379(1899), https://doi.org/10.1098/rstb.2022.0517

Parkinson's disease is a progressive neurological disorder, characterized by prominent movement dysfunction. The past two decades have seen a rapid expansion of our understanding of the genetic basis of Parkinson's, initially through the identificati... Read More about Common genetic risk for Parkinson's disease and dysfunction of the endo-lysosomal system.

Multi-ancestry genome-wide association meta-analysis of Parkinson's disease (2023)
Journal Article
Kim, J., Vitale, D., Otani, D., Lian, M., Heilbron, K., Aslibekyan, S., …Mata, I. (2023). Multi-ancestry genome-wide association meta-analysis of Parkinson's disease. Nature Genetics, https://doi.org/10.1038/s41588-023-01584-8

Although over 90 independent risk variants have been identified for Parkinson's disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-anal... Read More about Multi-ancestry genome-wide association meta-analysis of Parkinson's disease.

Differential LRRK2 Signalling and Gene Expression in WT-LRRK2 and G2019S-LRRK2 Mouse Microglia Treated with Zymosan and MLi2 (2023)
Journal Article
Nazish, I., Mamais, A., Mallach, A., Bettencourt, C., Kaganovich, A., Warner, T., …Bandopadhyay, R. (2023). Differential LRRK2 Signalling and Gene Expression in WT-LRRK2 and G2019S-LRRK2 Mouse Microglia Treated with Zymosan and MLi2. Cells, 13(1), https://doi.org/10.3390/cells13010053

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause autosomal dominant Parkinson's disease (PD), with the most common causative mutation being the LRRK2 p.G2019S within the kinase domain. LRRK2 protein is highly expressed in the human br... Read More about Differential LRRK2 Signalling and Gene Expression in WT-LRRK2 and G2019S-LRRK2 Mouse Microglia Treated with Zymosan and MLi2.

Lysosomal positioning regulates Rab10 phosphorylation at LRRK2 + lysosomes (2022)
Journal Article
Kluss, J. H., Beilina, A., Williamson, C. D., Lewis, P. A., Cookson, M. R., & Bonet-Ponce, L. (2022). Lysosomal positioning regulates Rab10 phosphorylation at LRRK2 + lysosomes. Proceedings of the National Academy of Sciences, 119(43), https://doi.org/10.1073/pnas.2205492119

Cytosolic sequestration of spatacsin by Protein Kinase A and 14-3-3 proteins (2022)
Journal Article
Cogo, S., Tomkins, J., Vavouraki, N., Giusti, V., Forcellato, F., Franchin, C., …Greggio, E. (2022). Cytosolic sequestration of spatacsin by Protein Kinase A and 14-3-3 proteins. Neurobiology of Disease, 174, https://doi.org/10.1016/j.nbd.2022.105858

Mutations in SPG11, encoding spatacsin, constitute the major cause of autosomal recessive Hereditary Spastic Paraplegia (HSP) with thinning of the corpus callosum. Previous studies showed that spatacsin orchestrates cellular traffic events through th... Read More about Cytosolic sequestration of spatacsin by Protein Kinase A and 14-3-3 proteins.

Regulation of mitophagy by the NSL complex underlies genetic risk for Parkinson’s disease at 16q11.2 and MAPT H1 loci (2022)
Journal Article
Soutar, M. P. M., Melandri, D., O’Callaghan, B., Annuario, E., Monaghan, A. E., Welsh, N. J., …Plun-Favreau, H. (2022). Regulation of mitophagy by the NSL complex underlies genetic risk for Parkinson’s disease at 16q11.2 and MAPT H1 loci. Brain, 145(12), 4349-4367. https://doi.org/10.1093/brain/awac325

Seventy-Two-Hour LRRK2 Kinase Activity Inhibition Increases Lysosomal GBA Expression in H4, a Human Neuroglioma Cell Line (2022)
Journal Article
Ruz, C., Alcantud, J., Vives, F., Arrebola, F., Hardy, J., Lewis, P., …Duran, R. (2022). Seventy-Two-Hour LRRK2 Kinase Activity Inhibition Increases Lysosomal GBA Expression in H4, a Human Neuroglioma Cell Line. International Journal of Molecular Sciences, 23(13), https://doi.org/10.3390/ijms23136935

A step forward for LRRK2 inhibitors in Parkinson's disease (2022)
Journal Article
Lewis, P. (2022). A step forward for LRRK2 inhibitors in Parkinson's disease. Science Translational Medicine, 14(648), https://doi.org/10.1126/scitranslmed.abq7374

A phase 1 clinical trial for kinase inhibitors targeting LRRK2 provides the foundation for testing the efficacy of LRRK2 kinase inhibitors in Parkinson's disease.

Dissecting the Phenotype and Genotype of PLA2G6‐Related Parkinsonism (2021)
Journal Article
Magrinelli, F., Mehta, S., Di Lazzaro, G., Latorre, A., Edwards, M. J., Balint, B., …Bhatia, K. P. (in press). Dissecting the Phenotype and Genotype of PLA2G6‐Related Parkinsonism. Movement Disorders, https://doi.org/10.1002/mds.28807

Background

Complex parkinsonism is the commonest phenotype in late-onset PLA2G6-associated neurodegeneration.

Objectives

The aim of this study was to deeply characterize phenogenotypically PLA2G6-related parkinsonism in the largest cohort ev... Read More about Dissecting the Phenotype and Genotype of PLA2G6‐Related Parkinsonism.

SORL1 mutation in a Greek family with Parkinson's disease and dementia (2021)
Journal Article
Xiromerisiou, G., Bourinaris, T., Houlden, H., Lewis, P. A., Senkevich, K., Hammer, M., …Hardy, J. (2021). SORL1 mutation in a Greek family with Parkinson's disease and dementia. Annals of Clinical and Translational Neurology, https://doi.org/10.1002/acn3.51433

In silico comparative analysis of LRRK2 interactomes from brain, kidney and lung (2021)
Journal Article
Verma, A., Ebanks, K., Fok, C., Lewis, P. A., Bettencourt, C., & Bandopadhyay, R. (2021). In silico comparative analysis of LRRK2 interactomes from brain, kidney and lung. Brain Research, 1765, 147503. https://doi.org/10.1016/j.brainres.2021.147503

Modelling the functional genomics of Parkinson’s disease in Caenorhabditis elegans: LRRK2 and beyond (2021)
Journal Article
Chandler, R., Cogo, S., Lewis, P., & Kevei, E. (2021). Modelling the functional genomics of Parkinson’s disease in Caenorhabditis elegans: LRRK2 and beyond. Bioscience Reports, 41(9), https://doi.org/10.1042/bsr20203672

Vesicle trafficking and pathways to neurodegeneration (2021)
Journal Article
Blackstone, C., Elwood, F., Plun-Favreau, H., & Lewis, P. A. (2021). Vesicle trafficking and pathways to neurodegeneration. Molecular Neurodegeneration, 16(1), https://doi.org/10.1186/s13024-021-00480-1

Abrogation of LRRK2 dependent Rab10 phosphorylation with TLR4 activation and alterations in evoked cytokine release in immune cells (2021)
Journal Article
Nazish, I., Arber, C., Piers, T. M., Warner, T. T., Hardy, J. A., Lewis, P. A., …Bandopadhyay, R. (2021). Abrogation of LRRK2 dependent Rab10 phosphorylation with TLR4 activation and alterations in evoked cytokine release in immune cells. Neurochemistry International, 147, 105070. https://doi.org/10.1016/j.neuint.2021.105070

From structure to ætiology: a new window on the biology of leucine-rich repeat kinase 2 and Parkinson's disease (2021)
Journal Article
Herbst, S., & Lewis, P. A. (2021). From structure to ætiology: a new window on the biology of leucine-rich repeat kinase 2 and Parkinson's disease. Biochemical Journal, 478(14), 2945-2951. https://doi.org/10.1042/bcj20210383

An integrated genomic approach to dissect the genetic landscape regulating the cell-to-cell transfer of α-synuclein (2021)
Journal Article
Kara, E., Crimi, A., Wiedmer, A., Emmenegger, M., Manzoni, C., Bandres-Ciga, S., …Aguzzi, A. (2021). An integrated genomic approach to dissect the genetic landscape regulating the cell-to-cell transfer of α-synuclein. Cell Reports, 35(10), 109189. https://doi.org/10.1016/j.celrep.2021.109189

Integrating protein networks and machine learning for disease stratification in the Hereditary Spastic Paraplegias (2021)
Journal Article
Vavouraki, N., Tomkins, J. E., Kara, E., Houlden, H., Hardy, J., Tindall, M. J., …Manzoni, C. (2021). Integrating protein networks and machine learning for disease stratification in the Hereditary Spastic Paraplegias. iScience, 102484. https://doi.org/10.1016/j.isci.2021.102484

Preclinical modeling of chronic inhibition of the Parkinson’s disease associated kinase LRRK2 reveals altered function of the endolysosomal system in vivo (2021)
Journal Article
Mamais, A., Cookson, M. R., Lewis, P. A., Manzoni, C., Li, Y., Mazza, M. C., & Kluss, J. H. (2021). Preclinical modeling of chronic inhibition of the Parkinson’s disease associated kinase LRRK2 reveals altered function of the endolysosomal system in vivo. Molecular Neurodegeneration, 16(1), https://doi.org/10.1186/s13024-021-00441-8

Identification of Candidate Parkinson Disease Genes by Integrating Genome-Wide Association Study, Expression, and Epigenetic Data Sets (2021)
Journal Article
Kia, D. A., Zhang, D., Guelfi, S., Manzoni, C., Hubbard, L., Reynolds, R. H., …United Kingdom Brain Expression Consortium (UKBEC) and the International Parkinson’s Disease Genomics Consortium (IPDGC). (2021). Identification of Candidate Parkinson Disease Genes by Integrating Genome-Wide Association Study, Expression, and Epigenetic Data Sets. JAMA Neurology, 78(4), 464. https://doi.org/10.1001/jamaneurol.2020.5257

IMPORTANCE Substantial genome-wide association study (GWAS) work in Parkinson disease (PD) has led to the discovery of an increasing number of loci shown reliably to be associated with increased risk of disease. Improved understanding of the underlyi... Read More about Identification of Candidate Parkinson Disease Genes by Integrating Genome-Wide Association Study, Expression, and Epigenetic Data Sets.