Author Type

Graduate Student

Date of Award

Spring 4-8-2026

Document Type

Thesis

Publication Status

Version of Record

Submission Date

April 2026

Department

Biomedical Science

College Granting Degree

Charles E. Schmidt College of Medicine

Department Granting Degree

Biomedical Science

Degree Name

Master of Science (MS)

Thesis/Dissertation Advisor [Chair]

Gregg. B. Fields

Abstract

Alzheimer’s Disease (AD) is a common neurodegenerative disease that is characterized by the accumulation of amyloid beta (Aβ) plaques and presence of neurofibrillary tangles (NFT) in the brain. Aβ oligomers are directly toxic to CNS synapses and can induce tau protein hyperphosphorylation, that causes NFT buildup. For these reasons, Aβ has been investigated as a therapeutic target, yet very few clinical trials have yielded effective drugs for AD treatment until now. Recently, the MT5-MMPmediated η-secretase pathway, which generates synaptotoxic Aη from amyloid precursor protein, has been reported (Wang et al 2024, Wilem et al 2015). Thus, pharmacologic inhibition of MT5-MMP could be an effective complementary therapeutic approach for AD treatment. With our prior MT5-MMP binding site knowledge, we synthesized phosphinate peptide inhibitors via the solid-phase peptide synthesis (SPPS) method as drug candidates for AD treatment, with several significant inhibitors resulting.

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