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Epigenetic inactivation of the autophagy-lysosomal system in appendix in Parkinson's disease.
Gordevicius, Juozas; Li, Peipei; Marshall, Lee L; Killinger, Bryan A; Lang, Sean; Ensink, Elizabeth; Kuhn, Nathan C; Cui, Wei; Maroof, Nazia; Lauria, Roberta; Rueb, Christina; Siebourg-Polster, Juliane; Maliver, Pierre; Lamp, Jared; Vega, Irving; Manfredsson, Fredric P; Britschgi, Markus; Labrie, Viviane.
Afiliación
  • Gordevicius J; Center for Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA. juozas.gordevicius@vai.org.
  • Li P; Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania. juozas.gordevicius@vai.org.
  • Marshall LL; Center for Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA.
  • Killinger BA; Center for Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA.
  • Lang S; Center for Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA.
  • Ensink E; Graduate College, Rush University Medical Center, Chicago, IL, USA.
  • Kuhn NC; Center for Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA.
  • Cui W; Center for Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA.
  • Maroof N; Department of Translational Neuroscience, College of Human Medicine, Michigan State University, Grand Rapids, MI, USA.
  • Lauria R; Center for Epigenetics, Van Andel Institute, Grand Rapids, MI, USA.
  • Rueb C; Roche Pharma Research and Early Development, Neuroscience Discovery, Roche Innovation Center, Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
  • Siebourg-Polster J; Roche Pharma Research and Early Development, Neuroscience Discovery, Roche Innovation Center, Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
  • Maliver P; Roche Pharma Research and Early Development, Neuroscience Discovery, Roche Innovation Center, Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
  • Lamp J; Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
  • Vega I; Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
  • Manfredsson FP; Department of Translational Neuroscience, College of Human Medicine, Michigan State University, Grand Rapids, MI, USA.
  • Britschgi M; Integrated Mass Spectrometry Unit, College of Human Medicine, Michigan State University, Grand Rapids, MI, USA.
  • Labrie V; Department of Translational Neuroscience, College of Human Medicine, Michigan State University, Grand Rapids, MI, USA.
Nat Commun ; 12(1): 5134, 2021 08 26.
Article en En | MEDLINE | ID: mdl-34446734
The gastrointestinal tract may be a site of origin for α-synuclein pathology in idiopathic Parkinson's disease (PD). Disruption of the autophagy-lysosome pathway (ALP) may contribute to α-synuclein aggregation. Here we examined epigenetic alterations in the ALP in the appendix by deep sequencing DNA methylation at 521 ALP genes. We identified aberrant methylation at 928 cytosines affecting 326 ALP genes in the appendix of individuals with PD and widespread hypermethylation that is also seen in the brain of individuals with PD. In mice, we find that DNA methylation changes at ALP genes induced by chronic gut inflammation are greatly exacerbated by α-synuclein pathology. DNA methylation changes at ALP genes induced by synucleinopathy are associated with the ALP abnormalities observed in the appendix of individuals with PD specifically involving lysosomal genes. Our work identifies epigenetic dysregulation of the ALP which may suggest a potential mechanism for accumulation of α-synuclein pathology in idiopathic PD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Apéndice / Autofagia / Epigénesis Genética / Lisosomas Límite: Animals / Female / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Apéndice / Autofagia / Epigénesis Genética / Lisosomas Límite: Animals / Female / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido