Synergistic Effects of Milk-Derived Exosomes and Galactose on alpha-Synuclein Pathology in Parkinson's Disease and Type 2 Diabetes Mellitus

DC FieldValueLanguage
dc.contributor.authorMelnik, Bodo C.
dc.date.accessioned2021-12-23T16:03:28Z-
dc.date.available2021-12-23T16:03:28Z-
dc.date.issued2021
dc.identifier.urihttps://osnascholar.ub.uni-osnabrueck.de/handle/unios/6019-
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 alpha-synucleinopathy associated with mitochondrial dysfunction, oxidative stress, deficient lysosomal clearance of alpha-synuclein (alpha-syn) and aggregation of misfolded alpha-syn. In T2D, alpha-syn promotes co-aggregation with islet amyloid polypeptide in pancreatic beta-cells. Prion-like vagal nerve-mediated propagation of exosomal alpha-syn from the gut to the brain and pancreatic islets apparently link both pathologies. Exosomes are critical transmitters of alpha-syn from cell to cell especially under conditions of compromised autophagy. This review provides translational evidence that milk exosomes (MEX) disturb alpha-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 beta-cells may enhance miRNA-148a/DNMT1-dependent overexpression of alpha-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 alpha-syn which is exported by exosome release. Via the vagal nerve and/or systemic exosomes, toxic alpha-syn may spread to dopaminergic neurons and pancreatic beta-cells linking the pathogenesis of PD and T2D.
dc.language.isoen
dc.publisherMDPI
dc.relation.ispartofINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
dc.subject&#945
dc.subject-synuclein
dc.subjectautophagy
dc.subjectBiochemistry & Molecular Biology
dc.subjectCHAIN AMINO-ACIDS
dc.subjectChemistry
dc.subjectChemistry, Multidisciplinary
dc.subjectdiabetes mellitus
dc.subjectDNA methyltransferase 1
dc.subjectELIMINATION CAPACITY
dc.subjectENVIRONMENTAL RISK-FACTORS
dc.subjectEXTRACELLULAR VESICLES
dc.subjectgalactose
dc.subjectGENE-EXPRESSION
dc.subjectISLET AMYLOID POLYPEPTIDE
dc.subjectmilk exosome
dc.subjectmilk microRNAs
dc.subjectMITOCHONDRIAL DYSFUNCTION
dc.subjectMPTP MOUSE MODEL
dc.subjectOXIDATIVE STRESS
dc.subjectParkinson&#8217
dc.subjects disease
dc.subjectSUBSTANTIA-NIGRA
dc.subjectvagal nerve
dc.titleSynergistic Effects of Milk-Derived Exosomes and Galactose on alpha-Synuclein Pathology in Parkinson's Disease and Type 2 Diabetes Mellitus
dc.typereview
dc.identifier.doi10.3390/ijms22031059
dc.identifier.isiISI:000615290300001
dc.description.volume22
dc.description.issue3
dc.contributor.orcid0000-0002-4501-1809
dc.identifier.eissn14220067
dc.publisher.placeST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
dcterms.isPartOf.abbreviationInt. J. Mol. Sci.
dcterms.oaStatusGreen Published, gold
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