Abstract
The aggregation of amyloid β (Aβ) peptide with subsequent formation of fibrils which deposit in senile plaques is considered one of the key triggers of Alzheimer's disease (AD). Molecules targeting the inhibition of Aβ fibrillation and/or the disruption of Aβ fibrils are thus promising approaches for the medical prevention and treatment of AD. However, amyloid formation is a complex process strongly influenced by the cellular environment, such as cell membranes, which may affect the effectiveness of therapeutic molecules. In this study, the effect of the vitamin B12 (VB12) on the formation and disaggregation of Aβ1-42 fibrils was investigated in the presence of artificial neuronal membranes mimicked by liposomes. Evidence showed that VB12 slows down the Aβ fibrillization and reduces the content of fibrils in aqueous solution. Moreover, the vitamin exhibited a strong ability to disrupt preformed fibrils. However, the presence of lipid vesicles compromised the VB12's antiamyloidogenic properties due to the competitive interaction of the vitamin with the lipid membrane and the Aβ peptide. Even so, VB12 was effective in inhibiting the fibril formation and disaggregating fibrils in the lipid membrane environment. Thereby, these results indicate that VB12 could be a promising molecule both for the prevention and cure of AD, thus warranting its study in animal models.
Full text
