Computational prospection of functional peptides from kefir microbiota with multitarget potential in Alzheimer’s disease

Abstract Alzheimer’s disease (AD) involves the accumulation of β-amyloid (Aβ), synaptic dysfunction, and neuronal loss. Given the limited efficacy of current treatments, natural bioactive molecules, such as peptides derived from kefir microbiota, are gaining interest. In silico analyses of two peptides from Brazilian kefir were carried out to assess their potential against key AD targets (Aβ, BACE1, and AChE). Docking studies showed that both peptides bind to fibrillar and monomeric Aβ, suggesting a possible preventive effect on aggregate formation. PepKLacM01 exhibited stronger binding to BACE1 and AChE, indicating potential inhibition, whereas PepKLacM02 displayed weaker and more peripheral interactions, yet maintained modulatory effects on Aβ aggregation. These findings suggest complementary mechanisms of action—aggregation prevention, enzyme inhibition, and modulation—and support further experimental validation for their potential therapeutic application in AD.