Abstract
Alzheimer’s disease (AD) is characterized by an increased plaque burden and tangle accumulation in the brain accompanied by extensive lipid alterations. Methylxanthines (MTXs) are alkaloids frequently consumed by dietary intake known to interfere with the molecular mechanisms leading to AD. Besides the fact that MTX consumption is associated with changes in triglycerides and cholesterol in serum and liver, little is known about the effect of MTXs on other lipid classes, which raises the question of whether MTX can alter lipids in a way that may be relevant in AD. Here we have analyzed naturally occurring MTXs caffeine, theobromine, theophylline, and the synthetic MTXs pentoxifylline and propentofylline also used as drugs in different neuroblastoma cell lines. Our results show that lipid alterations are not limited to triglycerides and cholesterol in the liver and serum, but also include changes in sphingomyelins, ceramides, phosphatidylcholine, and plasmalogens in neuroblastoma cells. These changes comprise alterations known to be beneficial, but also adverse effects regarding AD were observed. Our results give an additional perspective of the complex link between MTX and AD, and suggest combining MTX with a lipid-altering diet compensating the adverse effects of MTX rather than using MTX alone to prevent or treat AD.
Highlights
Methylxanthines (MTXs) are derivatives of the purine base xanthine and plant alkaloids, present in frequently consumed foods and beverages like coffee, cacao, chocolate and tea [1]
Aβ peptides that aggregate in senile plaques of Alzheimer’s disease (AD) patients, one important pathological hallmark of the disease [41]
We and others have found that MTXs, that are frequently consumed in almost every area of the world, decrease Aβ generation and Aβ aggregation [13,42], and MTXs have been reported to display health benefits in many neurodegenerative diseases involving cell death in the nervous system [12]
Summary
Methylxanthines (MTXs) are derivatives of the purine base xanthine and plant alkaloids, present in frequently consumed foods and beverages like coffee, cacao, chocolate and tea [1]. They are quickly absorbed in the gastrointestinal tract and distributed via the blood to different tissues, amongst others into the brain by crossing the blood–brain barrier [2]. MTXs antagonize cerebral adenosine receptors/purinergic P1 receptors because of their structural similarity with purine [5] Four subtypes of these receptors are reported (A1, A2A, A2B and A3), which are expressed in different cells of the human body [6,7].
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