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An integrated genomic approach to dissect the genetic landscape regulating the cell-to-cell transfer of α-synuclein.
Kara, Eleanna; Crimi, Alessandro; Wiedmer, Anne; Emmenegger, Marc; Manzoni, Claudia; Bandres-Ciga, Sara; D'Sa, Karishma; Reynolds, Regina H; Botía, Juan A; Losa, Marco; Lysenko, Veronika; Carta, Manfredi; Heinzer, Daniel; Avar, Merve; Chincisan, Andra; Blauwendraat, Cornelis; García-Ruiz, Sonia; Pease, Daniel; Mottier, Lorene; Carrella, Alessandra; Beck-Schneider, Dezirae; Magalhães, Andreia D; Aemisegger, Caroline; Theocharides, Alexandre P A; Fan, Zhanyun; Marks, Jordan D; Hopp, Sarah C; Abramov, Andrey Y; Lewis, Patrick A; Ryten, Mina; Hardy, John; Hyman, Bradley T; Aguzzi, Adriano.
Afiliação
  • Kara E; Institute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland; Department of Neurodegenerative disease, University College London, London WC1N 3BG, UK.
  • Crimi A; Institute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
  • Wiedmer A; Institute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
  • Emmenegger M; Institute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
  • Manzoni C; Department of Pharmacology, University College London School of Pharmacy, London WC1N 1AX, UK; School of Pharmacy, University of Reading, Reading RG6 6AP, UK.
  • Bandres-Ciga S; Laboratory of Neurogenetics, National Institutes of Health, Bethesda, MD 20814, USA.
  • D'Sa K; The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK; Department of Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, Lon
  • Reynolds RH; Department of Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London, UK; NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK.
  • Botía JA; Department of Neurodegenerative disease, University College London, London WC1N 3BG, UK; Departamento de Ingeniería de la Información y las Comunicaciones, Universidad de Murcia, Murcia 30100, Spain.
  • Losa M; Institute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
  • Lysenko V; Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich 8091, Switzerland.
  • Carta M; Institute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
  • Heinzer D; Institute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
  • Avar M; Institute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
  • Chincisan A; Institute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
  • Blauwendraat C; Laboratory of Neurogenetics, National Institutes of Health, Bethesda, MD 20814, USA.
  • García-Ruiz S; Department of Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London, UK; NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK.
  • Pease D; Institute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
  • Mottier L; Institute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
  • Carrella A; Institute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
  • Beck-Schneider D; Institute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
  • Magalhães AD; Institute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
  • Aemisegger C; Center for Microscopy and Image Analysis, University of Zurich, Zurich 8057, Switzerland.
  • Theocharides APA; Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich 8091, Switzerland.
  • Fan Z; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
  • Marks JD; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; Mayo Clinic Alix School of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
  • Hopp SC; Department of Pharmacology, UT Health San Antonio, San Antonio, TX 78229, USA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX 78229, USA.
  • Abramov AY; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK.
  • Lewis PA; Department of Neurodegenerative disease, University College London, London WC1N 3BG, UK; School of Pharmacy, University of Reading, Reading RG6 6AP, UK; Department of Comparative Biomedical Sciences, Royal Veterinary College, London NW1 0TU, UK.
  • Ryten M; Department of Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London, UK; NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK.
  • Hardy J; Department of Neurodegenerative disease, University College London, London WC1N 3BG, UK; UK Dementia Research Institute, University College London, London WC1N 3BG, UK; Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, 1 Wakefield Street, London WC1N 1PJ, UK; Institute for Advance
  • Hyman BT; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
  • Aguzzi A; Institute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland. Electronic address: adriano.aguzzi@usz.ch.
Cell Rep ; 35(10): 109189, 2021 06 08.
Article em En | MEDLINE | ID: mdl-34107263
Neuropathological and experimental evidence suggests that the cell-to-cell transfer of α-synuclein has an important role in the pathogenesis of Parkinson's disease (PD). However, the mechanism underlying this phenomenon is not fully understood. We undertook a small interfering RNA (siRNA), genome-wide screen to identify genes regulating the cell-to-cell transfer of α-synuclein. A genetically encoded reporter, GFP-2A-αSynuclein-RFP, suitable for separating donor and recipient cells, was transiently transfected into HEK cells stably overexpressing α-synuclein. We find that 38 genes regulate the transfer of α-synuclein-RFP, one of which is ITGA8, a candidate gene identified through a recent PD genome-wide association study (GWAS). Weighted gene co-expression network analysis (WGCNA) and weighted protein-protein network interaction analysis (WPPNIA) show that those hits cluster in networks that include known PD genes more frequently than expected by random chance. The findings expand our understanding of the mechanism of α-synuclein spread.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Comunicação Celular / Alfa-Sinucleína / Estudo de Associação Genômica Ampla / Mapas de Interação de Proteínas Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cell Rep Ano de publicação: 2021 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Comunicação Celular / Alfa-Sinucleína / Estudo de Associação Genômica Ampla / Mapas de Interação de Proteínas Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cell Rep Ano de publicação: 2021 Tipo de documento: Article