All Outputs (33)

Evidence suggesting that microglia make amyloid from neuronally expressed APP: a hypothesis (2025)
Journal Article
Hardy, J., & Lewis, P. (2025). Evidence suggesting that microglia make amyloid from neuronally expressed APP: a hypothesis. Molecular Neurodegeneration, 20(1), https://doi.org/10.1186/s13024-025-00847-8

While APP is largely neuonally expressed, A beta amyloid is largely produced by microglia as the clearance mechanisms for damaged membranes becomes overwhelmed.

Microglia contribute to the production of the amyloidogenic ABri peptide in familial British dementia (2024)
Journal Article
Arber, C., Casey, J., Crawford, S., Rambarack, N., Yaman, U., Wiethoff, S., Augustin, E., Piers, T., Price, M., Rostagno, A., Ghiso, J., Lewis, P., Revesz, T., Hardy, J., Pocock, J., Houlden, H., Schott, J., Salih, D., Lashley, T., & Wray, S. (2024). Microglia contribute to the production of the amyloidogenic ABri peptide in familial British dementia. Acta Neuropathologica, 148(1), https://doi.org/10.1007/s00401-024-02820-z

Mutations in ITM2B cause familial British, Danish, Chinese, and Korean dementias. In familial British dementia (FBD), a mutation in the stop codon of the ITM2B gene (also known as BRI2) causes a C-terminal cleavage fragment of the ITM2B/BRI2 protein... Read More about Microglia contribute to the production of the amyloidogenic ABri peptide in familial British dementia.

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., Auton, A., Babalola, E., Bell, R., Bielenberg, J., Bryc, K., Bullis, E., Cannon, P., Coker, D., Partida, G., Dhamija, D., Das, S., Elson, S., Eriksson, N., Filshtein, T., …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., Hardy, J., Lewis, P., Pocock, J., Cookson, M., & 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.

The emerging role of LRRK2 in tauopathies (2022)
Journal Article
Herbst, S., Lewis, P., & Morris, H. (2022). The emerging role of LRRK2 in tauopathies. Clinical Science, 136(13), 1071-1079. https://doi.org/10.1042/CS20220067

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., Tessari, I., Arrigoni, G., Cendron, L., Manzoni, C., Civiero, L., Lewis, P., & 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., D’Sa, K., Guelfi, S., Zhang, D., Pittman, A., Trabzuni, D., Verboven, A. H. A., Pan, K. S., Kia, D. A., Bictash, M., Gandhi, S., Houlden, H., Cookson, M. R., Kasri, N. N., Wood, N. W., …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., Manzoni, C., & 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., Basu, P., Kobylecki, C., Groppa, S., Hegde, A., Mulroy, E., Estevez‐Fraga, C., Arora, A., Kumar, H., Schneider, S. A., Lewis, P. A., Jaunmuktane, Z., Revesz, T., Gandhi, S., Wood, N. W., …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., Federoff, M., Khan, A., Spanaki, C., Hadjigeorgiou, G. M., Bonstanjopoulou, S., Fidani, L., Ermolaev, A., Gan‐Or, Z., Singleton, A., Vandrovcova, J., & 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

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

In silico comparative analysis of LRRK2 interactomes from brain, kidney and lung (2021)
Journal Article
Verma, A., Ebanks, K., Fok, C.-Y., 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

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., Pocock, J. M., & 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., D’Sa, K., Reynolds, R. H., Botía, J. A., Losa, M., Lysenko, V., Carta, M., Heinzer, D., Avar, M., Chincisan, A., Blauwendraat, C., García-Ruiz, S., Pease, D., Mottier, L., Carrella, A., …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