Oxidative stress causes neural damage and inhibits essential cellular
processes, such as synaptic transmission. Despite this knowledge, currently
available pharmaceutical agents cannot effectively protect neural cells from acute
oxidative stress elicited by strokes, heart attacks, and traumatic brain injuries in a
real life clinical setting. Our lab has developed an electrophysiology protocol to
identify novel drugs that protect an essential cellular process (neurotransmission)
from acute oxidative stress-induced damage. Through this doctoral dissertation,
we have identified three new drugs, including a Big K+ (BK) K+ channel blocker
(iberiotoxin), resveratrol, and a custom made resveratrol-like compound (fly2) that
protect synaptic function from oxidative stress-induced insults. Further developing
these drugs as neuroprotective agents may prove transformative in protecting the
human brain from acute oxidative stress elicited by strokes, heart attacks, and
traumatic brain injuries. Inhibiting the protein kinase G (PKG) pathway protects neurotransmission
from acute oxidative stress. This dissertation has expanded upon these findings
by determining that the PKG pathway and BK K+ channels function through
independent biochemical pathways to protect neurotransmission from acute
oxidative stress. Taken together, this dissertation has identified two classes of
compounds that protect neurotransmission from acute oxidative stress, including
resveratrol-like compounds (resveratrol, fly2) and a BK K+ channel inhibitor
(iberiotoxin). Further developing these drugs in clinical trials may finally lead to the
development of an effective neuroprotective agent. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection
| Identifer | oai:union.ndltd.org:fau.edu/oai:fau.digital.flvc.org:fau_40710 |
| Contributors | Bollinger, Wesley L. (author), Dawson-Scully, Ken (Thesis advisor), Florida Atlantic University (Degree grantor), Charles E. Schmidt College of Science, Department of Biological Sciences |
| Publisher | Florida Atlantic University |
| Source Sets | Florida Atlantic University |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation, Text |
| Format | 137 p., application/pdf |
| Rights | Copyright © is held by the author, with permission granted to Florida Atlantic University to digitize, archive and distribute this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder., http://rightsstatements.org/vocab/InC/1.0/ |
Page generated in 0.0022 seconds