title: Anti-aggregating effect of the naturally occurring dipeptide carnosine on aβ1-42 fibril formation.
abstract: Carnosine is an endogenous dipeptide abundant in the central nervous system, where by acting as intracellular pH buffering molecule, Zn/Cu ion chelator, antioxidant and anti-crosslinking agent, it exerts a well-recognized multi-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 dynamics of AD-related fibril formation remains uninvestigated. We considered the effects of carnosine on the formation of fibrils/aggregates of the amyloidogenic peptide fragment Aβ1-42, a major hallmark of AD injury. Atomic force microscopy and thioflavin T assays showed inhibition of Aβ1-42 fibrillogenesis in vitro and differences in the aggregation state of Aβ1-42 small pre-fibrillar structures (monomers and small oligomers) in the presence of carnosine. in silico molecular docking supported the experimental data, calculating possible conformational carnosine/Aβ1-42 interactions. Overall, our results suggest an effective role of carnosine against Aβ1-42 aggregation.
authors.affiliation: National Nanotechnology Laboratory of Consiglio Nazionale delle Ricerche, Istituto Nanoscienze Lecce, Lecce, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Aloisi
authors.forename: Amilcare
authors.initials: A
authors.lastname: Barca
authors.forename: Alessandro
authors.initials: A
authors.lastname: Romano
authors.forename: Sara
authors.initials: S
authors.lastname: Guerrieri
authors.forename: Carlo
authors.initials: C
authors.lastname: Storelli
authors.forename: Rosaria
authors.initials: R
authors.lastname: Rinaldi
authors.forename: Tiziano
authors.initials: T
authors.lastname: Verri
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D002336:Carnosine / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D011485:Protein Binding; D055503:Protein Multimerization / Q000187:drug effects*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D002336:Carnosine