Work

Influence of Ibuprofen on glycerophospholipids and sphingolipids in context of Alzheimer´s Disease

Year: 2025

Type: article

Abstract: Alzheimer's disease (AD) is a multifactorial disorder associated with neuroinflammation, elevated oxidative stress, lipid alterations as well as amyloid-deposits and the formation of neurofibrillary tangles. Ibuprofen, a globally used analgesic, is discussed to influence disease progression due to its anti-inflammatory effect. However, changes in lipid-homeostasis induced by Ibuprofen have not yet been analyzed. Here we investigate the effect of Ibuprofen on lipid classes known to be associated with AD. Ibuprofen treatment leads to a significant increase in phosphatidylcholine, sphingomyelin and triacylglyceride (TAG) species whereas plasmalogens, which are highly susceptible for oxidation, were significantly decreased. The observed alterations in phosphatidylcholine and sphingomyelin levels in presence of Ibuprofen might counteract the reduced phosphatidylcholine- and sphingomyelin-levels found in AD brain tissue with potential positive aspects on synaptic plasticity and ceramide-induced apoptotic effects. On the other hand, Ibuprofen leads to elevated TAG-level resulting in the formation of lipid droplets which are associated with neuroinflammation. Reduction of plasmalogen-levels might accelerate decreased plasmalogen-levels found in AD brains. Treatment of Ibuprofen in terms of lipid-homeostasis reveals both potentially positive and negative changes relevant to AD. Therefore, understanding the influence of Ibuprofen on lipid-homeostasis may help to understand the heterogeneous results of studies treating AD with Ibuprofen. • SH-SY5Y cells treated with Ibuprofen (IBU) revealed significant lipidome changes with relevance for Alzheimer’s disease (AD). • IBU incubation increased phosphatidylcholine and sphingomyeline levels, that were found to be decreased in AD brains. • Plasmalogens, known for their antioxidant properties, were reduced upon IBU treatment. • Triacylglyceride levels, major component of lipid droplets, accumulating in neurons in AD, were elevated after IBU treatment.

Source: Biomedicine & Pharmacotherapy

DOI: 10.1016/j.biopha.2025.117969