Synergistic Effects of Milk-Derived Exosomes and Galactose on α-Synuclein Pathology in Parkinson’s Disease and Type 2 Diabetes Mellitus 2021

[pattismith]

review about galactose hypothesis in Parkinson

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

Bodo C. Melnik

Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, D-49076 Osnabrück, Germany
Int. J. Mol. Sci. 2021, 22(3), 1059; https://doi.org/10.3390/ijms22031059

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. View Full-Text

 

[nerd]

Interesting to see more work on exosomes, especially the gut-vagus-brain link. What else may travel from the gut to the brain? Viral miRNA?

 

[pattismith]

This is a paper published in August 2021

Possible causes of Parkinson’s disease

James D. Adams1

Landmark4952.pdf (fbscience.com)