Year: 2010
Type: article
Abstract: Amyotrophic lateral sclerosis (ALS) has been studied for many years, yet there have been few innovations in its therapy.This debilitating and fatal disease has proven elusive to all but a few treatments.These treatments have only extended life for short periods of time in ALS patients and have not succeeded in arresting the progression of ALS.Our approach to understanding the oxidative stress behind the disease was studied using nanosensors that directly measure nitric oxide and peroxynitrite concentrations in vivo.Nitric oxide (NO) was thought of as a nuisance in ALS patients, but new studies show that nitric oxide removal proves ineffective at preventing ALS progression.We determined that NO performs a much more vital role in ALS than previously understood.Our conclusions show that after ALS onset, the enzyme responsible for NO production, nitric oxide synthase (NOS), remains in a dysfunctional state.This proved that NO in ALS neurons was already depleted and that peroxynitrite was prevalent, in terms of global concentration, within the neurons.Dysfunctional NOS accounted for increased production of superoxide, which is a common pathological symptom in most ALS cases.We determined that one main malignant affector in ALS is the peroxynitrite produced from dysfunctional NOS.As a corollary, the restoration of coupled NOS and NO production would prove beneficial.The NOS cofactor and co-substrate levels were proven to be in a diminished state, failing to provide sufficient production of nitric oxide the necessary skills to be a better scientist.His innovations and ideas are amazing and I am proud to have worked in his lab.I am grateful for the guidance he has given me and will always remember that.I would like to thank my committee members Dr. Blazyk, Dr. Jackson, Dr. Kieliszewski and Dr. Wu.I value the time you have spent helping me on my work, and I hope the skills that you have instilled in me get better with time.Your guidance is much appreciated.My lab mates have been unique to work with.I thank all of my past and current lab group for the encouragement and help in understanding my experiments.I especially would like to thank Dr. Ruslan Kubant.Your help was the best anyone could ask for and no matter where you end up, you will always be my friend.I couldn't have done it without you.My family and friends have been amazing in supporting me also.Mom, Dad, Jason and Leah
Author: Adam Jacoby
Institution: Ohio University
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2278567871