Synergistic Effects of Milk-Derived Exosomes and Galactose on α-Synuclein Pathology in Parkinson’s Disease and Type 2 Diabetes Mellitus
Abstract
:1. Introduction
2. Epidemiological Evidence
2.1. Milk Intake and Parkinson’s Disease
2.2. Milk Consumption and Type 2 Diabetes Mellitus
3. Milk: A Signaling System for Postnatal Growth and Differentiation
3.1. Milk Activates mTORC1 and Inhibits Autophagy
3.2. Milk Exosomes: Epigenetic Drivers of Developmental Genes
3.3. Milk Exosomes: Potential Drivers of α-Synuclein Expression and Transmission
3.4. Milk Exosomal miRNAs and SNCA Promoter Demethylation
4. Autophagy-Lysosome Pathway Controls Exosomal α-Synuclein Export
4.1. Milk Exosomes: Potential Modifiers of Chaperone-Mediated Autophagy
4.2. Bacterial Fermentation Degrades Milk Exosomes
5. Milk and Oxidative Stress
5.1. Galactose: Inducer of Oxidative Stress
5.2. Galactose: A Mitochondrial Stressor
5.3. Galactose: Inducer of miRNA-21
5.4. Oxidative Stress and Abelson Tyrosine Kinase Activation
5.5. Bacterial Fermentation Reduces Galactose Content of Dairy Products
5.6. Branched-Chain Amino Acids and Oxidative Stress
5.7. MiRNA-148a: Inhibitor of Mitochondrial Function and Autophagy
6. The α-Synuclein Link between Parkinson’s Disease and Type 2 Diabetes
6.1. α-Synuclein: Functional Component of β-Cells
6.2. Galactose Disturbs β-Cell α-Synuclein Homeostasis
7. Conclusions and Perspectives
8. Materials and Methods
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Total Dairy | Milk | Cheese | Yogurt | References |
---|---|---|---|---|
+ | + | Chen et al. (2002) [40] | ||
+ | Park et al. (2005) [41] | |||
+ | Sääksjärvi et al. (2013) [42] | |||
+ | Kyrozis et al. (2013) [43] | |||
+ | + | Jiang et al. (2014) [44] | ||
+ | Hughes et al. (2017) [45] | |||
+ | Olsson et al. (2020) [46] |
Agent | Predicted Functions | References |
---|---|---|
MEX miRNA-148a | Suppression of DNMT1, hypomethylation of SNCA with increased expression of α-syn in EECs and SN neuron. | [114,125] |
Suppression of AMPK activity increasing mTORC1 activity resulting in reduced ULK-1-mediated autophagy. | [206] | |
Suppression of PGC-1α reducing the expression of LC3-II, SQSTM1 and LAMP2 resulting in reduced autophagy. | [288] | |
Suppression of PGC-1α-mediated mitochondrial function with increased oxidative stress promoting α-syn aggregation. | [280,281,282,283,284,285] | |
MEX miRNA-21 | Reduction of DNMT1 activity, hypomethylation of SNCA with increased expression of α-syn in EECs and SN neurons. | [126] |
Suppression of LAMP2A resulting in reduced chaperone-mediated autophagy, accumulation of α-syn promoting α-syn aggregation. | [195,196,197] | |
Exosome lipids | Promotion of α-syn aggregation. | [149,158] |
Exosome membrane | α-syn binding to exosome outer membrane promoting exosome α-syn spreading. | [152] |
Pathogenic Factors | PD | References | T2D | References |
---|---|---|---|---|
Exosome traffic | + | [149,150,151,156,158,227,340,341,342,343] | + | [294,295,296,297,298,299,344,345,346] |
Vagal connectivity | + | [20,21,22,23,24,27,28,29] | + | [300,301,308,311] |
α-Synuclein aggregation ↑ | + | [134,145,191] | + | [311] |
Mitochondrial function ↓ | + | [13,179,184,221,225,228,262] | + | [328] |
Oxidative stress ↑ | + | [222,223,237,238,242] | + | [326] |
Autophagy ↓ | + | [94,154,177,178,183,185,188,189,190,191,192,196] | + | [327,328,329] |
Increased mTORC1 ↑ | + | [82,83,84,85] | + | [57,58,266] |
AMPK ↓ | + | [90] | + | [59,60] |
MiRNA-148a ↑ | + | [173] | + | [206] |
MiRNA-21 ↑ | + | [196] | + | [241,266] |
BCAA ↑ | + | [263,265] | + | [268,269,270,271,272,273] |
Metformin response | + | [89,90,91,92,93,265] | + | [61,62] |
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Melnik, B.C. Synergistic Effects of Milk-Derived Exosomes and Galactose on α-Synuclein Pathology in Parkinson’s Disease and Type 2 Diabetes Mellitus. Int. J. Mol. Sci. 2021, 22, 1059. https://doi.org/10.3390/ijms22031059
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. https://doi.org/10.3390/ijms22031059
Chicago/Turabian StyleMelnik, Bodo C. 2021. "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 22, no. 3: 1059. https://doi.org/10.3390/ijms22031059