College

College of Engineering and Polymer Science

Date of Last Revision

2023-05-05 05:25:10

Major

Chemical Engineering

Honors Course

4200 497-001/002

Number of Credits

3

Degree Name

Bachelor of Science

Date of Expected Graduation

Spring 2022

Abstract

Amyloid aggregation and microbial infection have been identified as the two main pathological risk factors that can result in amyloid diseases such as Alzheimer’s disease (AD), type II diabetes, and Parkinson’s disease. These two risk factors have been well studied separately, however only targeting one of these risk factors has shown to not be successful in preclinical trials since amyloid diseases are multifactorial. In this study, a new approach has been proposed to determine the effects of an antimicrobial and anti-amyloid aggregation approach by looking at the inhibition abilities of a heterocomplex of human α-defensin 6 (HD-6), whose secondary structure is rich in β-sheets, with beta amyloid (Aβ, associated with AD). Experimental results from thioflavin T assays, circular dichroism spectroscopy, atomic force microscopy, and cell and bacteria assays demonstrate that HD-6 could (1) prevent the aggregation and misfolding of amyloid peptides, (2) reduce cell toxicity due to amyloid peptides, and (3) retain its antimicrobial function after forming these heterocomplexes. Therefore, this study provides a new approach of repurposing an antimicrobial peptide as an amyloid inhibitor by blocking two interlinked pathological pathways and thus taking advantage of the dual functions of antimicrobial peptides to combat both amyloid aggregation and microbial infection.

Research Sponsor

Jie Zheng

First Reader

Bi-min Zhang Newby

Second Reader

Lu-Kwang Ju

Honors Faculty Advisor

Bi-min Zhang Newby

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