Lipids deficits

The function of the ALD protein is not fully understood, and knockout mice lacking it do not exhibit the severe CNS neurological deficits commonly associated with the human disease despite a similar accumulation of VLCFAs [26], Furthermore, the clinical variability in human patients cannot be accounted for by the severity of the biochemical abnormality or the nature of the gene defect. These observations, plus other data from mice with defects in VLCFA metabolism, raise the issue of whether the accumulation of VLCFAs in myelin is crucial to the pathological mechanisms or is an epiphenomenon. Unlike most other lipid-storage diseases, active ALD brain lesions are characterized by perivascular accumulation of lymphocytes. For this reason, it has been hypothesized that the severity of CNS pathology may relate to an autoimmune reaction that varies from patient to patient and... 

Such imbalanced antioxidant systems in schizophrenia could lead to oxidative stress- and ROS-mediated injury as supported by increased lipid peroxidation products and reduced membrane polyunsaturated fatty acids (PUFAs). Decrease in membrane phospholipids in blood cells of psychotic patients (Keshavan et al., 1993 Reddy et al., 2004) and fibroblasts from drug-naive patients (Mahadik et al., 1994) as well as in postmortem brains (Horrobin et al., 1991) have indeed been reported. It has also been suggested that peripheral membrane anomalies correlate with abnormal central phospholipid metabolism in first-episode and chronic schizophrenia patients (Pettegrewet al., 1991 Yao et al., 2002). Recently, a microarray and proteomic study on postmortem brain showed anomalies of mitochondrial function and oxidative stress pathways in schizophrenia (Prabakaran et al., 2004). Mitochondrial dysfunction in schizophrenia has also been observed by Ben-Shachar (2002) and Altar et al. (2005). As main ROS producers, mitochondria are particularly susceptible to oxidative damage. Thus, a deficit in glutathione (GSH) or immobilization stress induce greater increase in lipid peroxidation and protein oxidation in mitochondrial rather than in cytosolic fractions of cerebral cortex (Liu et al., 1996). 

MahadikSP, MukherjeeS, Scheffer R, CorrentiEE, Mahadik JS. 1998. Elevated plasma lipid peroxides at the onset of nonaffective psychosis. Biol Psychiatry 43 674-679. Malaspina D, Coleman E, Goetz RR, Harkavy-Friedman J, Corcoran C, et al. 2002. Odor identification, eye tracking and deficit syndrome schizophrenia. Biol Psychiatry 51 809-815. 

Rougemont M, Do KQ, Castagne V. 2003. A new model of glutathione deficit during development Effect of glutathione deficit on lipid peroxidation in the rat brain. J Neurosci Res 70 774-783. 

Abstract Alzheimer s disease (AD) is the most common cause of dementia in the elderly and is characterized by senile plaques, neurofibrillary tangles, synapse loss, and progressive neuronal deficits. There is an abundance of evidence suggesting that oxidative stress is involved in the pathogenesis of Alzheimer s disease. Several investigations have revealed the presence of oxidation products of proteins, lipids, and DNA in postmortem tissue from AD patients, indices that are indicative of increased oxidative stress. In the present review we discuss the role of protein oxidation in the brain of subjects with AD and MCI. 

Other abundant lipids in myelin are galactosylcerebrosides (Gal-C) and their sulfated derivatives (sulfatides). GalC represent 20% lipid dry weight in mature myelin. Immunological and chemical perturbation studies indicate that these lipids are involved in oligodendrocyte differentiation, myelin formation and myelin stability. These galactolipid-deficient animals exhibit severe tremor, hindlimb paralysis and display electro-physiological deficits in both CNS and PNS (Baumann and Pham-Dinh, 2001). 

Erythropoietin (EPO) promotes neurogenesis and neuroprotection. Maurice et al. [577] studied the effects of two formulations of EPO (rHu-EPO, and a low sialic form, Neuro-EPO) on Ap25 35 peptide toxicity. rHu-EPO and Neuro-EPO led to a significant prevention of A(>2S -induced learning deficits. Both EPO formulations prevented the induction of lipid peroxidation in the hippocampus and the Ap25 35-induced increase in Bax level, TNFa, and IL-ip production and decrease in Akt activation. 

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