Anti-aggregating effect of the naturally occurring dipeptide carnosine on a?1-42 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 A?1-42, a major hallmark of AD injury. Atomic force microscopy and thioflavin T assays showed inhibition of A?1-42 fibrillogenesis in vitro and differences in the aggregation state of A?1-42 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/A?1-42 interactions. Overall, our results suggest an effective role of carnosine against A?1-42 aggregation.

SUBMITTER: Aloisi A 

PROVIDER: S-EPMC3700870 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature