Synergistic Effects of Milk-Derived Exosomes and Galactose on alpha-Synuclein Pathology in Parkinson's Disease and Type 2 Diabetes Mellitus
DC Element | Wert | Sprache |
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dc.contributor.author | Melnik, Bodo C. | |
dc.date.accessioned | 2021-12-23T16:03:28Z | - |
dc.date.available | 2021-12-23T16:03:28Z | - |
dc.date.issued | 2021 | |
dc.identifier.uri | https://osnascholar.ub.uni-osnabrueck.de/handle/unios/6019 | - |
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 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.iso | en | |
dc.publisher | MDPI | |
dc.relation.ispartof | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | |
dc.subject | α | |
dc.subject | -synuclein | |
dc.subject | autophagy | |
dc.subject | Biochemistry & Molecular Biology | |
dc.subject | CHAIN AMINO-ACIDS | |
dc.subject | Chemistry | |
dc.subject | Chemistry, Multidisciplinary | |
dc.subject | diabetes mellitus | |
dc.subject | DNA methyltransferase 1 | |
dc.subject | ELIMINATION CAPACITY | |
dc.subject | ENVIRONMENTAL RISK-FACTORS | |
dc.subject | EXTRACELLULAR VESICLES | |
dc.subject | galactose | |
dc.subject | GENE-EXPRESSION | |
dc.subject | ISLET AMYLOID POLYPEPTIDE | |
dc.subject | milk exosome | |
dc.subject | milk microRNAs | |
dc.subject | MITOCHONDRIAL DYSFUNCTION | |
dc.subject | MPTP MOUSE MODEL | |
dc.subject | OXIDATIVE STRESS | |
dc.subject | Parkinson’ | |
dc.subject | s disease | |
dc.subject | SUBSTANTIA-NIGRA | |
dc.subject | vagal nerve | |
dc.title | Synergistic Effects of Milk-Derived Exosomes and Galactose on alpha-Synuclein Pathology in Parkinson's Disease and Type 2 Diabetes Mellitus | |
dc.type | review | |
dc.identifier.doi | 10.3390/ijms22031059 | |
dc.identifier.isi | ISI:000615290300001 | |
dc.description.volume | 22 | |
dc.description.issue | 3 | |
dc.contributor.orcid | 0000-0002-4501-1809 | |
dc.identifier.eissn | 14220067 | |
dc.publisher.place | ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND | |
dcterms.isPartOf.abbreviation | Int. J. Mol. Sci. | |
dcterms.oaStatus | Green Published, gold |
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geprüft am 21.05.2024