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bioRxiv2023

Combination of secondary plant metabolites and micronutrients against Alzheimer disease in a SH-SY5Y-APP695 cell model

Alzheimers disease (AD) is characterized by mitochondrial dysfunction, increased A{beta} levels and altered glycolysis. So far, there is no cure for AD, therefore it is important to take preventive or supportive action against AD. The cocktail (SC) tested in this study consists of the substances hesperetin (HstP), magnesium-orotate (MgOr) and folic acid (Fol), as well as the combination (KCC) of caffeine (Cof), kahweol (KW) and cafestol (CF). All the compounds showed positive results in the above mentioned fields of AD. The question arose whether a combination of all of them would also positively affect all three fields of AD. In this regard, SH-SY5Y-APP695 cells were incubated with SC and ATP levels, complex respiration, A{beta} levels, ROS levels, lactate and pyruvate levels were examined. The SC increased the endogenous respiration of the cells while significantly decreasing the A{beta}1-40 levels. SC has no significant effects on the other parameters. In summary, the combination of all compounds did not show the desired success that we hoped for, but the cocktail has potential to be further investigated. It is possible that the results will improve by changing the combinations or by adjusting the concentrations.

neuroscience↗

bioRxiv2023

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

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.

neuroscience↗