Phospholipase D in brain function and Alzheimer's disease

Abstract

Alzheimer’s disease is the most common neurodegenerative disorder. Although lipids are major constituents of brain, their role in Alzheimer’s disease pathogenesis is poorly understood. Much attention has been given to cholesterol, but growing evidence suggests that other lipids, such as phospholipids, might play an important role in this disorder. In this review, we will summarize the evidence linking phospholipase D, a phosphatidic acid-synthesizing enzyme, to multiple aspects of normal brain function and to Alzheimer’s disease. The role of phospholipase D in signaling mechanisms downstream of beta-amyloid as well as in the trafficking and processing of amyloid precursor protein will be emphasized.

The effect of exposure to chlorfenvinphos on lipid metabolism and apoptotic and necrotic cells death in the brain of rats

“…Moreover, the paper provides important data on the impact of these compounds on the brain activity of BChE and the relationship between this enzyme and AChE. The brain, being the lipid-rich tissue having relatively low antioxidative potential, is especially susceptible to the action of factors capable of inducing oxidative stress and disturbing lipid metabolism (Vance et al, 2005;Oliveira and Di Paolo, 2010;Ong et al, 2010). The nervous tissue due to high content of peroxidizable unsaturated lipids and high oxygen utilization is more vulnerable to peroxidative damage than other organs.…”

“…An important causative role in the development of diseases of the nervous system has been played by the oxidative/antioxidative imbalance and disorders in lipid metabolism in the nervous tissue as well as a decrease in the number of the nervous cells (Refolo et al, 2000;Vance et al, 2005;Martins et al, 2009;Oliveira and Di Paolo, 2010;Ong et al, 2010;Ziv and Melamed, 2010). OP compounds have been reported to cause oxidative stress with consequent lipid peroxidation and to induce apoptosis and necrosis in the brain under acute and chronic exposure (Brocardo et al, 2005;Üner et al, 2006;Kaur et al, 2007;Dwivedi and Flora, 2011;El-Demerdash, 2011;Solati et al, in press).…”

“…The increased concentrations of TCh and TG with the elevated TCh/PL ratio, and decreased PL concentration observed in the brain of the rats exposed to chlorfenvinphos allow for the conclusion that this pesticide might decrease fluidity and disturb function of cellular membranes of the nervous cells. PL and cholesterol are the most abundant lipid components of cellular membranes in the nervous tissue and they play a central role in the physiology and pathology of the CNS (Blasiak, 1993;Refolo et al, 2000;Björkhem and Meaney, 2004;Dietschy and Turey, 2004;Pandya et al, 2004;Vance et al, 2005;Martins et al, 2009;Oliveira and Di Paolo, 2010;Ong et al, 2010). PL influence multiple aspects of the physiology of the nervous cells, including cytoskeleton regulation, membrane transport, and signal transduction (Oliveira and Di Paolo, 2010).…”

The role and regulation of phospholipase d in brain insulin signaling pathway

“…Активність ФЛД у неокортексі щурів визначали за утворенням фосфатидилетанолу (ФЕТ), фосфоліпіду, який утворюється винятково ФЛД через трансфосфатидилю-вання за наявності 50-300 ммоль/л етанолу [11,13]. ФЕТ, на відміну від фосфатидної кислоти, метаболізується дуже повільно і з огляду на це є індикатором активації ФЛД в стимульованих клітинах.…”

Lipids and Alzheimer's disease

“…On a related subject, Oster and Pillot provide an overview of the multiple protective actions that one specific EFA, docosahexaenoic acid, may exert in the context of Aβ-induced neurotoxicity [9]. Oliveira and Di Paolo discuss the role of phospholipase D (PLD) in the brain and suggest that that through the regulation of APP processing (and other pathways), PLD isozymes may contribute to AD neurodegeneration [10].…”