Polar lipids modify Alzheimer's Disease pathology by reducing astrocyte pro-inflammatory signaling through platelet-activating factor receptor (PTAFR) modulation.

BACKGROUND: Pro-inflammatory processes triggered by the accumulation of extracellular amyloid beta (Aß) peptides are a well-described pathology in Alzheimer's disease (AD). Activated astrocytes surrounding Aß plaques contribute to inflammation by secreting proinflammatory factors. While astrocytes may phagocytize Aß and contribute to Aß clearance, reactive astrocytes may also increase Aß production. Therefore, identifying factors that can attenuate astrocyte activation and neuroinflammation and how these factors influence pro-inflammatory pathways is important for developing therapeutic and preventive strategies in AD. Here, we identify the platelet-activating factor receptor (PTAFR) pathway as a key mediator of astrocyte activation. Intriguingly, several polar lipids (PLs) have exhibited anti-inflammatory protective properties outside the central nervous system through their inhibitory effect on the PTAFR pathway. Thus, we additionally investigated whether different PLs also exert inhibitory effects on the PAF pathway in astrocytes and whether their presence influences astrocytic pro-inflammatory signaling and known AD pathologies in vitro. METHODS: PLs from salmon and yogurt were extracted using novel food-grade techniques and their fatty acid profile was determined using LC/MS. The effect of PLs on parameters such as astrocyte activation and generation of oxygen species (ROS) was assessed. Additionally, effects of the secretome of astrocytes treated with these polar lipids on aged neurons was measured. RESULTS: We show that PLs obtained from salmon and yogurt lower astrocyte activation, the generation of reactive oxygen species (ROS), and extracellular Aß accumulation. Cell health of neurons exposed to the secretome of astrocytes treated with salmon-derived PLs and Aß was less affected than those treated with astrocytes exposed to Aß only. CONCLUSION: Our results highlight a novel underlying mechanism, why consuming PL-rich foods such as fish and dairy may reduce the risk of developing dementia and associated disorders.

Oil from Mullet Roe Byproducts: Effect of Oil Extraction Method on Human Erythrocytes and Platelets.

Background: The valorization of byproducts to obtain high nutritional value foods is of utmost importance for our planet where the population is booming. Among these products are oils rich in ω-3 fatty acids produced from fishery byproducts. Recently, mullet roe oil from roe byproducts was produced that was rich in the ω-3 fatty acids eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA). Oils are customarily characterized for their composition and degree of oxidation but little is known of their biological effects, especially the effect of the extraction method. Methods: The purpose of this study was to evaluate the effects of freshly extracted mullet roe oil from mullet roe byproducts and the effect of the extraction method on human red blood cells (hRBCs) and platelets. To this end, the hemocompatibility (cytotoxicity), oxidative effects, and erythrocyte membrane changes were examined after 1 and 24 h of incubation. Antiplatelet effects were also assessed in vitro. Results: The expeller press oil extraction method and alcalase-assisted extraction produced the most biocompatible oils, as shown by hemocompatibility measurements and the absence of erythrocyte membrane alterations. Solvent extracts and protease-assisted extraction oils resulted in the rupture of red blood cells at different examined dilutions, creating hemolysis. Conclusions: It seems that the proper functioning of oil-erythrocyte interactions cannot be explained solely by ROS. Further investigations combining chemical analysis with oil-cell interactions could be used as an input to design high nutritional value oils using green extraction technologies. All samples exhibited promising antiplatelet and antiblood clotting effects in vitro.

The Role of Dietary Lipids in Cognitive Health: Implications for Neurodegenerative Disease.

Neurodegenerative diseases are a group of disorders characterised by progressive loss of brain function. The most common of these is Alzheimer's disease, a form of dementia. Intake of macro- and micro-nutrients impacts brain function, including memory, learning, mood, and behaviour. Lipids, particularly phospholipids and sphingolipids, are crucial structural components of neural tissues and significantly affect cognitive function. The importance of functional foods in preventing cardiovascular disease is well-documented in the current literature. However, the significance of such foods for central nervous system health and neurodegenerative diseases is less recognized. Gut microbiome composition affects cognitive health and function, and dietary lipids are known to influence gut health. Thus, this review will discuss different sources of dietary lipids and their effect on cognitive functioning and their interaction with the gut microbiome in the context of neurodegenerative disease.

Targeting the Platelet-Activating Factor Receptor (PAF-R): Antithrombotic and Anti-Atherosclerotic Nutrients.

Platelet-activating factor (PAF) is a lipid mediator that interacts with its receptor (PAF-R) to carry out cell signalling. However, under certain conditions the binding of PAF to PAF-R leads to the activation of pro-inflammatory and prothrombotic pathways that have been implicated in the onset and development of atherosclerotic cardiovascular diseases (CVD) and inflammatory diseases. Over the past four decades, research has focused on the identification and development of PAF-R antagonists that target these inflammatory diseases. Research has also shown that dietary factors such as polar lipids, polyphenols, and other nutrient constituents may affect PAF metabolism and PAF-R function through various mechanisms. In this review we focus on the inhibition of PAF-R and how this may contribute to reducing cardiovascular disease risk. We conclude that further development of PAF-R inhibitors and human studies are required to investigate how modulation of the PAF-R may prevent the development of atherosclerotic cardiovascular disease and may lead to the development of novel therapeutics.