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.
|Commitee:||Dawson-Scully, Kenneth, Hughes, Colin, Ja, William, Macleod, Gregory|
|School:||Florida Atlantic University|
|School Location:||United States -- Florida|
|Source:||DAI-B 80/02(E), Dissertation Abstracts International|
|Keywords:||BK channels, Hydrogen peroxide, Iberiotoxin, Neuroprotection, Resveratrol, Synaptic transmission|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be