Home Department: Bioengineering
Mentor: Annelise Barron (Bioengineering)

"Targeting the TLR4–NLRP3 Inflammatory Cascade with the Host Defense Peptide LL-37"

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by significant neurotoxic inflammation and progressive cognitive decline, representing a major unmet clinical need. Emerging evidence implicates the NLRP3 inflammasome and its downstream inflammatory cytokines as critical mediators of AD pathology. This neuroinflammatory response can be driven by Toll-like receptor 4 (TLR4), which is activated by AD-associated biomarkers such as amyloid-beta. While the innate immune peptide LL-37 is known to inhibit general TLR4 signaling, its effect on the downstream NLRP3-dependent inflammatory pathway in microglial cells remains unexplored. This project aims to rigorously establish LL-37 as a targeted inhibitor of TLR4-induced NLRP3 activation, thereby defining a novel anti-inflammatory strategy for AD treatment.