Carnosine (b-Ala-L-His) is an endogenous bioactive dipeptide, specifically abundant in muscle and central nervous system (CNS). Many physiological/biochemical features linked to cell homeostasis have been shown for carnosine: in particular, by acting as intracellular pH buffer modulator, Zn/Cu ion chelator, antioxidant and anti-cross-linking agent for proteins, carnosine is thought to work as a multifunctionally protective and homeostatic molecule for neuronal and non-neuronal cells in the CNS. Due to its properties, variations in carnosine content have already been evaluated in tissues and fluids from patients with neurodegenerative conditions/pathologies, such as Alzheimer's Disease (AD).

In this work, we investigated the effects of carnosine on aberrant amyloid aggregates and fibril formation by the amyloidogenic peptide fragment Ab1-42, a major hallmark of the AD injury in nervous cells. Scanning force microscopy and thioflavin T assay were used to show the differences in aggregation state of Ab1-42 at pH 7.4, in the presence and absence of carnosine as modulator. For the first time, it was shown that carnosine inhibits Ab1-42 fibrillogenesis, suggesting an anti-aggregating effect of carnosine on Ab1-42 polymerization in the lag phase of fibril formation in vitro. An in silico study of molecular docking well supported the experimental evidences.

Overall, our results give hints for a protective role of carnosine in the context of Alzheimer's Disease.