PLoS ONE (Jan 2013)

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

  • Alessandra Aloisi,
  • Amilcare Barca,
  • Alessandro Romano,
  • Sara Guerrieri,
  • Carlo Storelli,
  • Rosaria Rinaldi,
  • Tiziano Verri

DOI
https://doi.org/10.1371/journal.pone.0068159
Journal volume & issue
Vol. 8, no. 7
p. e68159

Abstract

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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.