TAILIEUCHUNG - Báo cáo khoa học: Lipid-induced conformational transition of the amyloid core fragment Ab(28–35) and its A30G and A30I mutants

The interaction of theb-amyloid peptide (Ab) with neuronal membranes could play a key role in the pathogenesis of Alzheimer’s disease. Recent studies have focused on the interactions of Aboligomers to explain the neuronal toxicity accompanying Alzheimer’s disease. | ỊFEBS Journal Lipid-induced conformational transition of the amyloid core fragment Ap 28-35 and its A30G and A30I mutants Sureshbabu Nagarajan1 Kirubagaran Ramalingam2 P. Neelakanta Reddy1 Damiano M. Cereghetti3 E. J. Padma Malar4 and Jayakumar Rajadas1 1 Bio-Organic and Neurochemistry Laboratory CentralLeather Research Institute Adyar Chennai India 2 NationalInstitute of Ocean Technology Pallikaranai Chennai India 3 Department of Medicine Stanford University CA USA 4 NationalCentre for Ultrafast Processes University of Madras Chennai India Keywords amyloid core fragment Ap 28-35 hydrophobicity and sheet propensity membrane disruption and neurotoxicity mutation negatively charged lipids Correspondence J. Rajadas Bio-Organic and Neurochemistry Laboratory Central Leather Research Institute Adyar Chennai 600 020 Fax 91 44 24911589 Tel 91 44 24911386 extn 324 E-mail karkuvi77@ Received 9 November 2007 revised 8 February 2008 accepted 5 March 2008 doi The interaction of the b-amyloid peptide Ab with neuronal membranes could play a key role in the pathogenesis of Alzheimer s disease. Recent studies have focused on the interactions of Ab oligomers to explain the neuronal toxicity accompanying Alzheimer s disease. In our study we have investigated the role of lipid interactions with soluble Ab 28-35 wild-type and its mutants A30G and A30I in their aggregation and conformational preferences. CD and Trp fluorescence spectroscopic studies indicated that immediately on dissolution these peptides adopted a random coil structure. Upon addition of negatively charged 1 2-dipalmitoyl-syn-glycero-3-phospho-rac- glycerol sodium salt PG lipid the wild-type and A30I mutant underwent reorganization into a predominant b-sheet structure. However no conformational changes were observed in the A30G mutant on interaction with PG. In contrast the presence of zwitterionic 1 2-dipalmitoyl-syn-glycero-3-phosphatidylcholine PC lipid had no effect on the

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