Microbial infection and amyloid aggregation are considered as pathological risk factors for initiating and promoting the onset and progression of amyloid diseases. Discovery of antimicrobial peptides to inhibit both microbial infection and amyloid aggregation allows to examine a new antimicrobial protection hypothesis. However, functional and structural correlations between antimicrobial and amyloid peptides remain largely unknown. In this work, we are the first to identify a class of host defense antimicrobial peptide of α-defensins, which serve as general inhibitors to not only prevent the aggregation and misfolding of different amyloid peptides of amyloid-β (Aβ, associated with Alzheimer’s disease), human islet amyloid polypeptide (hIAPP, associated with type II diabetes), and human calcitonin (hCT, associated with osteoporosis and Paget’s diseases), but also reduce amyloid-induced cell toxicity. Such inhibition effect of α-defensins mainly stems from their cross-interactions with amyloid peptides via similar β-structure associations. In parallel, α-defensins still preserved their intrinsic antimicrobial properties against four common microorganisms, demonstrating their anti-inflammation function. This work demonstrates a new mechanistic insight into the dual protection roles of antimicrobial peptides/agents in developing an effective treatment strategy for amyloid disease.

Antimicrobial α-defensins as broad-spectrum Inhibitors against amyloid formation

ACS Spring Meeting 2021

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