engleski

Membrane lipids and neurodegeneration

Precise control and regulation of brain lipids metabolism is required during complex processes of dynamic rebuilding and remodelling of neuronal membranes (neurite outgrowth, synaptogenesis, myelination). Also, it has been confirmed that lipid metabolism is altered in neurodegeneration and that changes in membrane properties and structural-functional integrity contribute to neurodegeneration process. The alterations of membrane physicochemical properties are not merely a consequence of primary pathology, but may be involved in early pathogenesis of the disease. It is of particular interest to investigate the intermolecular interactions within highly organized lipid microdomaines - lipid rafts - enriched in cholesterol, sphingolipids and specific protein molecules. Here we focus to gangliosides, membrane glycosphingolipids bearing sialic acid residues, which are attributed with diverse functions such as intercellular interactions, cell recognition, neurotransmission, and signal transduction. The highest concentration and variability of ganglioside structures are found in the human brain. Specific temporal and regional distribution of brain gangliosides has been reported. Moreover, gangliosides may serve as markers of neurodevelopmental stages, aging and neurodegeneration. Brain ganglioside content and composition as well as ganglioside metabolism are altered in Alzheimer’s disease. It appears that alterations of membrane ganglioside composition are involved in the early pathogenesis of Alzheimer’s disease through documented effects on amyloid precursor protein proteolytic processing and amyloid aggregation. Investigations of glycolipid metabolic alterations which accompany neurodegenerative disorders provide insight into pathogenetic mechanisms and enable recognition of diagnostic markers as well as molecular structures interfering with cascade of pathological events.

membrane lipids; neurodegeneration

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