Anti-aggregating effect of the naturally occurring dipeptide carnosine on aβ1-42 fibril formation

• Published in: PloS one 2013-07, Vol.8 (7), p.e68159
• Main Authors: Aloisi, Alessandra, Barca, Amilcare, Romano, Alessandro, Guerrieri, Sara, Storelli, Carlo, Rinaldi, Rosaria, Verri, Tiziano
• Format: Article
• Language: English
• Subjects: Agglomeration; Alzheimer's disease; Amyloid - chemistry; Amyloid - metabolism; Amyloid - ultrastructure; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - metabolism; Amyloidogenesis; Antioxidants; Atomic force microscopy; Biochemistry; Biology; Carnosine; Carnosine - chemistry; Carnosine - pharmacology; Central nervous system; Crosslinking; Dose-Response Relationship, Drug; Efficiency; Environmental science; Fibrillogenesis; Humans; Laboratories; Ligands; Medicine; Microscopy; Models, Molecular; Molecular Conformation; Molecular docking; Molecular Docking Simulation; Monomers; Nanotechnology; Neurodegenerative diseases; Neurotoxicity; Oligomers; Peptides; pH effects; Protein Binding; Protein Multimerization - drug effects; Proteins; R&D; Research & development; Zinc
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0068159

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.