Abstract
Background: Alzheimer’s disease (AD) progresses silently, with pathological changes such as amyloid-beta (Aβ) accumulation occurring years before cognitive symptoms emerge. Early intervention is considered critical to modifying disease progression. However, conventional therapeutics often lack pathological specificity and cause systemic side effects, highlighting the need for disease-responsive strategies. Methods: We designed a BACE1-cleavable peptide precursor that self-assembles into nanofibers in Aβ-rich environments. Enzyme-triggered assembly was characterized using dynamic light scattering (DLS) and Thioflavin T (ThT) fluorescence. Neuroprotective effects were assessed via MTT assay and qPCR of inflammatory markers. Results: The responsive peptide formed stable nanostructures upon BACE1 activation, significantly suppressed Aβ aggregation, improved neuronal viability, and reduced IL-1β expression. Conclusion: This study validates the use of enzyme-responsive peptide nanofibers as a selective and multifunctional therapeutic strategy for early intervention in Alzheimer’s disease, combining disease-environment activation with anti-aggregation, anti-inflammatory, and cognitive protective effects.
Keywords: Alzheimer’s disease; enzyme-responsive peptide; self-assembly; nanofibers; Aβ aggregation