Anti-Aggregating Effect of the Naturally Occurring Dipeptide Carnosine on Aβ1-42 Fibril Formation.docVIP

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Anti-Aggregating Effect of the Naturally Occurring Dipeptide Carnosine on Aβ1-42 Fibril Formation.doc

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Anti-Aggregating Effect of the Naturally Occurring Dipeptide Carnosine on Aβ1-42 Fibril Formation

Anti-AggregatingEffectoftheNaturallyOccurring DipeptideCarnosineonAb1-42FibrilFormation AlessandraAloisi1.,AmilcareBarca2.,AlessandroRomano2,SaraGuerrieri1,2¤,CarloStorelli2, RosariaRinaldi1,3*,TizianoVerri2* 1National Nanotechnology Laboratory (NNL) of Consiglio Nazionale delle Ricerche (CNR) – Istituto Nanoscienze Lecce, Lecce, Italy, 2Department of Biological and EnvironmentalSciencesandTechnologies(DiSTeBA),UniversityofSalento,Lecce,Italy,3MathematicsandPhysics‘‘E.DeGiorgi’’Department,UniversityofSalento,Lecce, Italy Abstract Carnosine is an endogenous dipeptide abundant in the central nervous system, where by acting as intracellular pH bufferingmolecule,Zn/Cuionchelator,antioxidantandanti-crosslinkingagent,itexertsawell-recognizedmulti-protective homeostatic function for neuronal and non-neuronal cells. Carnosine seems to counteract proteotoxicity and protein accumulation in neurodegenerative conditions, such as Alzheimer’s Disease (AD). However, its direct impact on the dynamicsofAD-relatedfibrilformationremainsuninvestigated.Weconsideredtheeffectsofcarnosineontheformationof fibrils/aggregatesoftheamyloidogenicpeptidefragmentAb1-42,amajorhallmarkofADinjury.Atomicforcemicroscopy andthioflavinTassaysshowedinhibitionofAb1-42fibrillogenesisinvitroanddifferencesintheaggregationstateofAb1- 42smallpre-fibrillarstructures(monomersandsmalloligomers)inthepresenceofcarnosine.insilicomoleculardocking supported the experimental data, calculating possible conformational carnosine/Ab1-42 interactions. Overall, our results suggestaneffectiveroleofcarnosineagainstAb1-42aggregation. Citation:AloisiA,BarcaA,RomanoA,GuerrieriS,StorelliC,etal.(2013)Anti-AggregatingEffectoftheNaturallyOccurringDipeptideCarnosineonAb1-42Fibril Formation.PLoSONE8(7):e68159.doi:10.1371/journal.pone.0068159 Editor:SalvadorVentura,UniversitatAuto`nomadeBarcelona,Spain ReceivedNovember5,2012;AcceptedMay31,2013;PublishedJuly3,2013 Copyright: ? 2013 Aloisi etal. This is an open-access article distributed