Antimicrobial Peptides as Cross-Seeding Modulators at the Neurodegenerative-Infectious Interface

Area of Science:

• Biochemistry
• Immunology
• Molecular Biology

Background:

• Antimicrobial peptides (AMPs) traditionally function as innate immune effectors.
• AMPs share structural and functional similarities with pathogenic amyloids.
• Emerging evidence links AMPs to the modulation of amyloid aggregation.

Purpose of the Study:

• To highlight the emerging role of AMPs as cross-seeding modulators of amyloid fibrillization.
• To summarize mechanistic insights into AMP-amyloid interactions.
• To present advances in engineering AMP-derived inhibitors for amyloid diseases.

Main Methods:

• Review of recent studies on AMPs and amyloid aggregation.
• Mechanistic analysis of β-sheet-rich AMPs engaging amyloidogenic targets.
• Summary of design strategies for engineering dual-function AMPs.

Main Results:

• AMPs can inhibit or promote amyloid fibrillization based on structural context.
• AMP-amyloid cross-seeding contributes to a feedback loop linking infections, inflammation, and neurodegeneration.
• Engineered AMP inhibitors demonstrate enhanced specificity, stability, and therapeutic potential.

Conclusions:

• AMPs represent a novel class of cross-seeding modulators with implications for protein misfolding diseases.
• Dual-function AMPs offer a promising therapeutic strategy for Alzheimer's, type 2 diabetes, and systemic amyloidosis.
• Further research is needed for data-driven design, delivery optimization, and clinical development of AMPs.