Novel nNOS Inhibitors Targets Aβ Oligomer-Driven pathology in Alzheimer’s Disease

Session Number

2

Advisor(s)

Dr. Raghad Nowar, Northwestern University

Location

A123

Discipline

Biology

Start Date

15-4-2026 11:10 AM

End Date

15-4-2026 11:55 AM

Abstract

Alzheimer’s Disease (AD) is a neurodegenerative disorder that affects nearly 57 million individuals worldwide. An effect of the disease is characterized by a disruption in the signal from the production of Nitric Oxide (NO), which highly contributes to negative symptoms that AD patients experience. In neurons, nitric oxide is mainly produced by a compound called neuronal nitric oxide synthase (nNOS). Therefore, there has been production to find therapeutic strategies to target nNOS production. nNOS is one of three isozymes that is present in neurons and responsible for NO production. We will assess the cellular efficacy of newly synthesized derivatives of an inhibitor that is selective only to nNOS by using live-cell fluorescence detection with DAF-FM dye. DAF-FM dye is a cell-permeable fluorescent probe that detects NO in the brain cells; when it interacts with NO, a chemical reaction resulting in a highly fluorescent derivative occurs. We also add Amyloid-beta oligomers (AβO) to the cells to induce neurotoxic effects, and with the selective inhibitor we tested the viability through fluorescence. This study focused on testing newly synthesized nNOS inhibitors to potentially decrease excessive nNOS activity that could lead to neuronal damage in Alzheimer’s Disease

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Apr 15th, 11:10 AM Apr 15th, 11:55 AM

Novel nNOS Inhibitors Targets Aβ Oligomer-Driven pathology in Alzheimer’s Disease

A123

Alzheimer’s Disease (AD) is a neurodegenerative disorder that affects nearly 57 million individuals worldwide. An effect of the disease is characterized by a disruption in the signal from the production of Nitric Oxide (NO), which highly contributes to negative symptoms that AD patients experience. In neurons, nitric oxide is mainly produced by a compound called neuronal nitric oxide synthase (nNOS). Therefore, there has been production to find therapeutic strategies to target nNOS production. nNOS is one of three isozymes that is present in neurons and responsible for NO production. We will assess the cellular efficacy of newly synthesized derivatives of an inhibitor that is selective only to nNOS by using live-cell fluorescence detection with DAF-FM dye. DAF-FM dye is a cell-permeable fluorescent probe that detects NO in the brain cells; when it interacts with NO, a chemical reaction resulting in a highly fluorescent derivative occurs. We also add Amyloid-beta oligomers (AβO) to the cells to induce neurotoxic effects, and with the selective inhibitor we tested the viability through fluorescence. This study focused on testing newly synthesized nNOS inhibitors to potentially decrease excessive nNOS activity that could lead to neuronal damage in Alzheimer’s Disease