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bioRxiv · 10.1101/2023.04.20.537643

THE EFFECT OF SELECTED COFFEE CONSTITUENTS ON MITOCHON-DRIAL DYSFUNCTION IN AN EARLY ALZHEIMER DISEASE CELL MODEL

Babylon, L.·Limbeck, M. T.·Eckert, G. P.
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Abstract

Alzheimer disease (AD) is an emerging medical problem worldwide without any cure yet. By 2050, more than 152 million people will be affected. AD is characterized by mitochondrial dys-function (MD) and increased amyloid beta (A{beta}) levels. Coffee is one of the most commonly consumed beverages. It has many bioactive and neuroprotective ingredients of which caffeine (Cof), kahweohl (KW) and cafestol (CF) shows a variety of pharmacological properties such as anti-inflammatory and neuroprotective effects. Effects of Cof, KW, and CF were tested in a cel-lular model of AD on MD and A{beta}. SH-SY5Y-APP695 cells were incubated with 50{micro}M Cof, 1{micro}M CF and 1{micro}M KW for 24h. The energetic metabolite ATP was determined using a luciferase-catalyzed bioluminescence assay. The activity of mitochondrial respiration chain complexes was assessed by high-resolution respirometry using a Clarke electrode. Expression levels genes were deter-mined using quantitative real-time polymerase chain reaction (qRT-PCR). The levels of amyloid {beta}-protein (A{beta}1-40) were measured using homogeneous time-resolved fluorescence (HTRF). ROS levels, cAMP levels, and peroxidase activity were determined using a fluorescence assay. The combination of Cof, KW and CF significantly increased ATP levels. The combination had neither a significant effect on MMP, on activity of respiration chain complexes, nor on A{beta}1-40 levels. cAMP levels were slightly increased after incubation with the combination, but not the peroxi-dase activity. Pyruvate levels and the lactate-pyruvate-ration but not lactate levels were signifi- cantly enhanced. No effect was seen on the expression level of lactate dehydrogenase and py-ruvate dehydrogenase kinase. In some experiments we have tested the single substances. They showed significant results especially in ATP, lactate and pyruvate values compared to the con-trol. The combinations have a lesser effect on mitochondrial dysfunction in cells and none on A{beta} production. Whereas ATP levels and pyruvate levels were significantly increased. This suggests a change in glycolysis in neuronal cells harbouring human genes relevant for AD.

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Babylon, L., Limbeck, M. T., Eckert, G. P.. 2023-04-20. THE EFFECT OF SELECTED COFFEE CONSTITUENTS ON MITOCHON-DRIAL DYSFUNCTION IN AN EARLY ALZHEIMER DISEASE CELL MODEL. https://doi.org/10.1101/2023.04.20.537643

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