Modulation of phospholipid asymmetry in synaptosomal membranes by the lipid peroxidation products, 4-hydroxynonenal and acrolein: implications for Alzheimer's disease.

Membrane lipid bilayer asymmetry is maintained by the ATP-dependent enzyme flippase. An early signal of synaptosomal apoptosis is the loss of phospholipid asymmetry and the appearance of phosphatidylserine (PS) in the outer leaflet of the membrane. Two highly reactive products of lipid peroxidation, 4-hydroxynonenal (HNE) and acrolein, both elevated in Alzheimer's disease (AD) brain, have been shown to induce apoptosis and disrupt cellular ion homeostasis.

Derivatives of xanthic acid are novel antioxidants: application to synaptosomes.

Xanthic acids have long been known to act as reducing agents. Recently, D609, a tricyclodecanol derivative of xanthic acid, has been reported to have anti-apoptotic and anti-inflammatory properties that are attributed to specific inhibition of phosphatidyl choline phospholipase C (PC-PLC). However, because oxidative stress is involved in both of these cellular responses, the possibility that xanthates may act as antioxidants was investigated in the current study.

Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer's disease brain contribute to neuronal death.

Amyloid beta-peptide [Abeta(1-42)] is central to the pathogenesis of Alzheimer's disease (AD), and the AD brain is under intense oxidative stress, including membrane lipid peroxidation. Abeta(1-42) causes oxidative stress in and neurotoxicity to neurons in mechanisms that are inhibited by Vitamin E and involve the single methionine residue of this peptide. In particular, Abeta induces lipid peroxidation in ways that are inhibited by free radical antioxidants.

Lipid peroxidation and protein oxidation in Alzheimer's disease brain: potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress.

Amyloid beta-peptide (A(beta)) is heavily deposited in the brains of Alzheimer's disease (AD) patients, and free radical oxidative stress, particularly of neuronal lipids and proteins, is extensive. Recent research suggests that these two observations may be linked by A(beta)-induced oxidative stress in AD brain. This review summarizes current knowledge on phospholipid peroxidation and protein oxidation in AD brain, one potential cause of this oxidative stress, and consequences of A(beta)-induced lipid peroxidation and protein oxidation in AD brain.

Apolipoprotein E modulates Alzheimer's Abeta(1-42)-induced oxidative damage to synaptosomes in an allele-specific manner.

Several functional differences have been reported among the three human e2, e3, and e4 alleles of apolipoprotein E (apoE). One functional difference lies in the antioxidant potential of these alleles; e4 has the poorest potential. Interestingly, e4 also correlates with increased oxidative damage in the Alzheimer's disease (AD) brain, which may explain why the inheritance of the e4 allele is a risk factor for the onset of AD.