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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dc.creatorMelnik, Bodo C.-
dc.date.accessioned2021-06-03T12:10:54Z-
dc.date.available2021-06-03T12:10:54Z-
dc.date.issued2021-01-31-
dc.identifier.citationMelnik 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.urihttps://osnadocs.ub.uni-osnabrueck.de/handle/urn:nbn:de:gbv:700-202106034907-
dc.description.abstractEpidemiological 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.relationhttps://doi.org/10.3390/ijms22031059ger
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectautophagyeng
dc.subjectDNA methyltransferase 1eng
dc.subjectdiabetes mellituseng
dc.subjectgalactoseeng
dc.subjectmilk exosomeeng
dc.subjectmilk microRNAseng
dc.subjectoxidative stresseng
dc.subjectParkinson’s diseaseeng
dc.subjectα-synucleineng
dc.subjectvagal nerveeng
dc.subject.ddc610 - Medizin, Gesundheitger
dc.titleSynergistic Effects of Milk-Derived Exosomes and Galactose on α-Synuclein Pathology in Parkinson’s Disease and Type 2 Diabetes Mellituseng
dc.typeEinzelbeitrag in einer wissenschaftlichen Zeitschrift [article]ger
orcid.creatorhttps://orcid.org/0000-0002-4501-1809-
dc.identifier.doi10.3390/ijms22031059-
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