Involvement of Plasmalogens in Neurological Disorders

Neural membranes are complex, well-organized, and highly specialized structures involved in receiving, processing, transporting, and transmitting information, not only from the plasma membrane to the nucleus, but also from one cell to another through chemical mediators generated during the catabolism of various glycerophospholipids (Guan et al., 1999; Farooqui and Horrocks, 2007). Neural membranes are highly interactive and dynamic. These properties facilitate optimal interactions of lipid mediators with transmembrane proteins, receptors, and ion channels and maintain normal brain function and adaptive responses (Farooqui et al., 1995; Farooqui and Horrocks, 2004). Although very little is known about the regulation of lipid dynamics in neural membranes, this process has been reported to link with the biosynthesis, metabolism, and transport of individual molecular species of glycerophospholipid (Farooqui and Horrocks, 2007). The catabolism of neural membrane glycerophospholipids, including plasmalogens, involves phospholipases, whose activities are modulated by receptors and ion channels. Plasmalogens provide neural membranes with suitable stability, fluidity, and permeability. They serve as storage depot and precursors for eicosanoids, docosanoids, and platelet activating factor.

In neural membranes, the maintenance of lipid asymmetry requires up to 20– 26% consumption of ATP (Purdon et al., 2002; Purdon and Rapoport, 2007). This high rate of ATP consumption includes 1.4% of net brain ATP consumption for de novo synthesis of ether lipids, 5% for recycling of fatty acids within glycerophospholipid, 7.7% for maintaining membrane asymmetries of charged aminophospholipids, and about 12% for maintaining the phosphorylation state and de novo synthesis of inositol containing phospholipids involving phosphatidylinositol signaling (Purdon and Rapoport, 2007). Much of the remaining ATP maintains the distribution and transport of ions and activities of membrane-bound enzymes and ion channels. The high rate of ATP consumption is consistent with the role of glycerophospholipids in neural cell signaling, apoptosis, and membrane-associated processes such as membrane fusion, anchoring, and recycling (Purdon and Rapoport, 2007). At present, no information is available on ATP consumption during traffick- ing and sorting of various glycerophospholipids in neurons, astrocytes, oligodendrocytes, and microglial glial cells. The situation on ATP consumption during glycerophospholipid trafficking and sorting becomes more complex at the subcellular level (endoplasmic reticulum, Golgi apparatus, nucleus, etc.) of various cell types of neural cells in normal brain and brains from patients with neural trauma and neurodegenerative diseases.


Fetal Alcohol Syndrome Ether Lipid Fatty Aldehyde Zellweger Syndrome Peroxisomal Disorder 
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