Epigenetic inactivation of the autophagy–lysosomal system in appendix in Parkinson’s disease
- Resource Type
- Authors
- Markus Britschgi; Viviane Labrie; Irving E. Vega; Lee Marshall; Nazia Maroof; Juliane Siebourg-Polster; Nathan C. Kuhn; Peipei Li; Wei Cui; Juozas Gordevičius; Jared Lamp; Sean Lang; Fredric P. Manfredsson; Roberta Lauria; Christina Rueb; Elizabeth Ensink; Bryan A. Killinger; Pierre Maliver
- Source
- Nature Communications, Vol 12, Iss 1, Pp 1-18 (2021)
Nature Communications
Nature communications, Berlin : Nature research, 2021, vol. 12, iss. 1, art. no. 5134, p. [1-18]
- Subject
- Male
musculoskeletal diseases
Parkinson's disease
Science
General Physics and Astronomy
Biology
Epigenetic inactivation
autophagy
Appendix
digestive system
General Biochemistry, Genetics and Molecular Biology
Deep sequencing
Article
Epigenesis, Genetic
Mice
Protein Aggregates
stomatognathic system
medicine
Autophagy
Animals
Humans
Epigenetics
Epigenetics in the nervous system
Gene
Epigenesis
Gastrointestinal tract
Multidisciplinary
musculoskeletal, neural, and ocular physiology
Brain
Parkinson Disease
General Chemistry
DNA Methylation
medicine.disease
musculoskeletal system
Mice, Inbred C57BL
DNA methylation
Cancer research
alpha-Synuclein
Female
Lysosomes
Neuroscience
- Language
- English
- ISSN
- 2041-1723
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.
Dysfunction of the gastrointestinal system, and to the autophagy lysososmal pathway (ALP) have been reported in Parkinson’s disease. Here the authors report epigenetic disruption of ALP related genes in the appendix of individuals with Parkinson’s disease.