Publication Date

2017

Document Type

Thesis

Committee Members

Sherif Elbasiouny (Committee Chair), Mark Rich (Committee Member), Keiichiro Susuki (Committee Member)

Degree Name

Master of Science (MS)

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a fatal, adult-onset progressive degenerative motor neuron disease that is characterized by muscle atrophy and weakness due to the loss of upper and lower motor neurons. Average survival time for individuals diagnosed with the disease is three to five years; currently there is no cure and only one drug approved by the Food and Administration (FDA). Scientists have proposed various theories in order to solve the mystery which surrounds ALS. One of these theories hypothesizes how hyperexcitability and excitotoxicity leads to the death of motor neurons. In this study, we will address ways of combatting the effects of hyperexcitability as well as excitotoxicity by targeting a specific channel type. The channels in question are small conductance calcium activated potassium channels (SK channels). We chose to target these channels because they directly affect the medium after-hyperpolarization (mAHP) of the cell which controls firing rate. We postulate that SK channels are being altered in such a way that cell firing rate has been increased, leading to phenotypes associated with the disease such as abnormal excitability, mitochondrial dysfunction, axonal loss motor impairment, muscle atrophy as well as excitotoxicity, thus leading to the spread of motor neuron death. Upon administration with a specific SK channel activator in the form of CyPPA; improvements in motor function and survival were found. These improvements suggest that SK channels are indeed viable drug targets and specific SK channel activators may be treatment options for individuals suffering from ALS.

Page Count

101

Department or Program

Department of Neuroscience, Cell Biology, and Physiology

Year Degree Awarded

2017

ORCID ID

0000-0002-7798-5907

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