Synergistic Effects of Milk-Derived Exosomes and Galactose on α-Synuclein Pathology in Parkinson’s Disease and Type 2 Diabetes Mellitus
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Full metadata record
DC Field | Value | Language |
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dc.creator | Melnik, Bodo C. | - |
dc.date.accessioned | 2021-06-03T12:10:54Z | - |
dc.date.available | 2021-06-03T12:10:54Z | - |
dc.date.issued | 2021-01-31 | - |
dc.identifier.citation | Melnik BC.: Synergistic Effects of Milk-Derived Exosomes and Galactose on α-Synuclein Pathology in Parkinson’s Disease and Type 2 Diabetes Mellitus. International Journal of Molecular Sciences. 2021; 22(3):1059. | ger |
dc.identifier.uri | https://osnadocs.ub.uni-osnabrueck.de/handle/urn:nbn:de:gbv:700-202106034907 | - |
dc.description.abstract | Epidemiological studies associate milk consumption with an increased risk of Parkinson’s disease (PD) and type 2 diabetes mellitus (T2D). PD is an α-synucleinopathy associated with mitochondrial dysfunction, oxidative stress, deficient lysosomal clearance of α-synuclein (α-syn) and aggregation of misfolded α-syn. In T2D, α-syn promotes co-aggregation with islet amyloid polypeptide in pancreatic β-cells. Prion-like vagal nerve-mediated propagation of exosomal α-syn from the gut to the brain and pancreatic islets apparently link both pathologies. Exosomes are critical transmitters of α-syn from cell to cell especially under conditions of compromised autophagy. This review provides translational evidence that milk exosomes (MEX) disturb α-syn homeostasis. MEX are taken up by intestinal epithelial cells and accumulate in the brain after oral administration to mice. The potential uptake of MEX miRNA-148a and miRNA-21 by enteroendocrine cells in the gut, dopaminergic neurons in substantia nigra and pancreatic β-cells may enhance miRNA-148a/DNMT1-dependent overexpression of α-syn and impair miRNA-148a/PPARGC1A- and miRNA-21/LAMP2A-dependent autophagy driving both diseases. MiRNA-148a- and galactose-induced mitochondrial oxidative stress activate c-Abl-mediated aggregation of α-syn which is exported by exosome release. Via the vagal nerve and/or systemic exosomes, toxic α-syn may spread to dopaminergic neurons and pancreatic β-cells linking the pathogenesis of PD and T2D. | eng |
dc.relation | https://doi.org/10.3390/ijms22031059 | ger |
dc.rights | Attribution 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | autophagy | eng |
dc.subject | DNA methyltransferase 1 | eng |
dc.subject | diabetes mellitus | eng |
dc.subject | galactose | eng |
dc.subject | milk exosome | eng |
dc.subject | milk microRNAs | eng |
dc.subject | oxidative stress | eng |
dc.subject | Parkinson’s disease | eng |
dc.subject | α-synuclein | eng |
dc.subject | vagal nerve | eng |
dc.subject.ddc | 610 - Medizin, Gesundheit | ger |
dc.title | Synergistic Effects of Milk-Derived Exosomes and Galactose on α-Synuclein Pathology in Parkinson’s Disease and Type 2 Diabetes Mellitus | eng |
dc.type | Einzelbeitrag in einer wissenschaftlichen Zeitschrift [article] | ger |
orcid.creator | https://orcid.org/0000-0002-4501-1809 | - |
dc.identifier.doi | 10.3390/ijms22031059 | - |
Appears in Collections: | FB08 - Hochschulschriften Open-Access-Publikationsfonds |
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File | Description | Size | Format | |
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ijms_Melnik_2021.pdf | 1,55 MB | Adobe PDF | ijms_Melnik_2021.pdf View/Open |
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