Lipid peroxidation, neurodegenerative

Numerous in vitro studies have implicated ROS in neuronal death [Leonardi and Mytilineou, 1998], and different markers of oxidative stress are found in postmortem examination of brain tissues from patients with neurodegenerative disorders [Sayre et al., 2001], DNA oxidation, protein oxidation, and lipid peroxidation have been reported in brain regions containing neurofibrillary tangles and senile plaques from Alzheimer s disease (AD) patients [Lovell and Markesbery, 2007 Polidori et al., 2007], Dopaminergic neurons in the substantia nigra of brains of Parkinson s disease (PD) patients also exhibit hallmarks of oxidative stress [Giasson et al., 2002]. 

Lipid peroxidation is one of the major sources of free-radical mediated injury that directly damages membranes and generates a number of secondary products. In particular, markers of lipid peroxidation have been found to be elevated in brain tissues and body fluids in several neurodegenerative diseases, and the role of lipid peroxidation has been extensively discussed in the context of their pathogenesis. Peroxidation of membrane lipids can have numerous effects, including increased membrane rigidity, decreased activity of membrane-bound enzymes (e.g., sodium pumps), altered activity of membrane receptors, and altered permeability [Anzai et al., 1999 Yehuda et al., 2002], In addition to effects on phospholipids, lipid-initiated radicals can also directly attack membrane proteins and induce lipid-lipid, lipid-protein, and protein-protein cross-linking, all of which obviously have effects on membrane function. 

Montine, K.S., Quin, J.F., Zhang, J., Fessel, J.P., Roberts, L.J., Morrow, J.D., Montine, T.J. (2004). Isoprostanes and related products of lipid peroxidation in neurodegenerative diseases. Chem. Phys. Lipids 128 117-24. 

Hall, E.D. (1992) Novel inhibitors of iron-dependent lipid peroxidation for neurodegenerative disorders. Ann. Neurol. 32 (Suppl.) 137-142. 

Oxygen radicals and their derivatives can be deadly to cells. The hydroxyl radical causes oxidative damage to proteins and DNA. It also forms lipid peroxides and malondialdehyde from membrane lipids containing polyunsaturated fatty acids. In some cases, free radical damage is the direct cause of a disease state (e.g., tissue damage initiated by exposure to ionizing radiation). In neurodegener-ative diseases, such as Parkinson s disease, or in ischemia-reperfusion injury,... 

Oxidative stress is closely associated with the pathogenesis of ALS. Several antioxidants including vitamin E, acetylcysteine, methylcobalamin, and glutathione have been tested in clinical trials of ALS. Coenzyme QIO (CoQlO) is an antioxidant and mitochondrial cofactor (Fig. 9.12). It not only prevents lipid peroxidation but also stabilizes the Ca " channels. Its oral administration increases CoQlO levels in mitochondria. CoQlO produces promising effects in ALS transgenic mice and in clinical trials for neurodegenerative diseases other than ALS. Phase II clinical trial of CoQlO in ALS patients indicate that this dmg is ineffective in producing beneficial effects in ALS patients (Levy et al., 2006), and opinions on phase III trials have been controversial (Kaufmann et al., 2009). 

Redox Proteomics, Lipid Peroxidation, and Neurodegenerative Disorders.330... 

IMPORTANCE OF LIPID PEROXIDATION AND ITS EFFECTS IN NEURODEGENERATIVE DISEASES... 

Lipids are readily available throughout the body therefore, lipid peroxidation is a common phenomenon. Currently, there are no absolute diagnostic biomaricers for the early diagnosis of any neurodegenerative disease. As lipid peroxidation can have detrimental effects on proteins, DNA, RNA, and mitochondria, the study of this oxidative modification and its role on neurodegenerative diseases is paramount. This chapter will highlight the role of lipid peroxidation in neurodegenerative disease mechanisms as well as the role of mitochondrial involvement in brain disorders. 

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