Oxidant damage of neurones, whose membranes are protected by the glutathione and CoA systems, play a significant role in the pathogenesis of neurodegenerative pathology. Active studies have been carried out on the genetic defect of pantothenate kinase (ATP:D-pantothenate-4'-phosphotransferase, EC 2.7.1.33, the key enzyme of CoA biosynthesis) which is referred to as pantothenate kinase associated neurodegeneration (PKAN). It has been found that PKAN is a heterogenous neurologic pathology including the autosomal recessive syndrome of extrapyramidal system injury and the so-called HARP syndrome (hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, palladial degeneration). This genetic defect first revealed in systemic neurodegeneration occurs due to mutation of the gene encoding mitochondrial pantothenate kinase on locus 20p12.3. Both the experiments, in which neurodegenerative pathology was simulated by either administration of lipopolysaccharide (LPS), or its combination with aluminium neurotoxicosis, or by injections of cholinotoxine AF64A, and the studies in vitro using neuromembranous preparations showed:

– development of neuronal degeneration in the frontal cortex and hyppocampus with pronouncedly impaired glutathione redox state and CoA system (pantothenate kinase activity being stable);

– aggravation of glutathione redox state and disturbances in the CoA system by LPS administered concomitantly with sequestration of free CoA by valproate pretreatment;

– pantothenate-dependent mechanisms for stabilization of neuronal membranes in oxidative stress were revealed that were mediated by functional relationships between the glutathione system and the thioldisulfide (redox) status and the phospholipid membranous composition;

– a modulatory role of L-methionine (as a precursor of L-cysteine, a CoA biosynthetic substrate) and L-lipoic acid (a glutathione reductase reaction activator) in realization of pantothenate (CoA) protective properties of the CoA biosynthetic system was proved.

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1. Biotransformation of 4'-phosphopantothenic acid in brain structures after its intracerebroventricular administration
2. Effect of body saturation with selenomethionine on glutathione peroxidases activities in acute alcohol intoxication