Degree Type

Creative Component

Semester of Graduation

Spring 2021

Department

Biomedical Sciences

First Major Professor

Anumantha Kanthasamy

Degree(s)

Master of Science (MS)

Major(s)

Biomedical Sciences

Abstract

Alzheimer’s disease is a progressive neurodegenerative disease that affects noradrenergic neurons in the locus coeruleus and dopaminergic neurons in the substantia nigra. These neurons transmit norepinephrine and dopamine via broad projections to different regions of the brain involved in cognition, memory, and reward. Decrease in norepinephrine and dopamine signaling is associated with LC and SN axon degeneration and Aβ amyloid, senile plaques, and hyperphosphorylated pre-tangled tau protein accumulation. Moreover, NE and DA decrease the production of reactive oxygen species, ameliorate mitochondrial oxidative damage, and protect against neurodegeneration. The catecholamines can further limit oxidative transformation that induces Aβ aggregation and Aβ mediated toxicity. This was demonstrated through memory and reward dysfunction in multiple studies of the 5xFAD mouse model of AD. These pathological changes are major targets for drug development and disease-modifying treatments of AD. Additionally, the cholinergic system is also known the be the most important current therapeutic target involving the use of acetylcholinesterase inhibitors that were proven clinically useful in the treatment of Alzheimer’s disease and other related dementia. Overall, the goal of this literature review is to describe the mechanisms of how deficiency of norepinephrine and dopamine leads to neurodegeneration and ultimately Alzheimer’s disease.

Copyright Owner

Sabri, Lara

File Format

PDF

Embargo Period (admin only)

4-22-2022

1

Available for download on Friday, April 22, 2022

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