Oxidative Stress By: Andrew Lorusso

Overview Alvaro Estevez an associate professor at the University of Central Florida led a multi-university team that may have uncovered the truth regarding oxidative stress. This discovery may lead to the development of many new therapies for a wide range of illnesses. Some conditions and diseases that may be impacted by this discovery: Amyotrophic Lateral Sclerosis (ALS) Stroke victims Spinal Cord Injuries (SCI)

What is Oxidative Stress? “Oxidation” is a chemists term for the removal of electrons from an atom or molecule. When the body breaks down food we used oxygen from the air we breath to produce energy. From this natural process there are byproducts produced which in some cases can be dangerous. Some of these byproducts are known as free radicals. In an effort to become electronically stable the free radicals will rip electrons from any molecule within reach. This produces a chain reaction which eventually fizzles out, but in the process leaves a wake of destruction. The burden placed on the organism by these free radicals is known as Oxidative stress.

Past knowledge It was known that oxidative stress damaged cells leading to neuron death which lead to inflammation and aging. Scientists believed that the cells effected by oxidative stress began to crumble and fall apart. Oxidative stress had also been thought to have some connection to cancer.

Hsp90 Heat shock protein 90 (Hsp90) is a “chaperone” protein that helps other proteins to fold properly, stabilize them against heat stress, and also aid in protein degradation. Found to aid proteins required for tumor growth. Which has led to research for new cancer drugs. When the body is exposed to elevated temperatures Heat shock proteins numbers are doubled in an effort to protect cells from the heat. Hsp90 is one of the most common of the Hsp particles and is number 90 due to its weight of roughly 90 kiloDaltons.

The Discovery Oxidative Stress has a more direct impact on only certain parts of the cell. Oxidative stress damages a specific “chaperone” cell protein called Hsp90. When a a form of oxidative stress called tyrosine nitration modifies the Hsp90 protein, turning it into an “executioner” shutting it down. This modified protein is found in a wide range of disease studies.

Key to this experiment Researchers were able to use new methods to genetically engineer nitrotyrosine into Hsp90 This new method made it possible for researchers to pin down the exact areas of damage. Current researchers hope this knowledge will aid future scientists in the identification of drugs that could interrupt this process.

What is a Stroke? A stroke or “brain attack” occurs when a blood clot blocks an artery or if a blood vessel breaks, interrupting blood flow to an area of the brain. When either take place, brain cells begin to die, leading to brain damage. With this brain damage, comes the loss of the ability to control certain brain functions. These functions depend upon the area of the brain that the brain damage occurred. How does it relate? This process of cell death is thought to be caused by the modified Hsp90 proteins.

What is ALS? Ambyotrophic Lateral Sclerosis (ALS) also known as Lou Gehrig’s disease is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. Motor neurons which run from the brain to the spinal cord and from the spinal cord to muscles throughout the body begin to die. As the motor neurons die the connection from the brain to the muscles is lost. Ultimately leading to the patient becoming paralyzed and in most cases, eventually to death. How does it relate? As the cells begin to die a high concentration of the altered Hsp90 proteins were found in the patients affected by ALS.

What are Spinal Cord Injuries? Spinal Cord Injuries (SCI) are injuries to the spinal cord that are caused by trauma rather than disease. The spinal cord carries signals to and from the brain to the muscles throughout the body. Upon injuring the spinal cord the signals are interrupted below the site of the injury. Depending on the severity of the injury, the patient may become paralyzed. (no signal can go beyond the injury) How does it relate? The modified Hsp90 protein was found to be in high concentration in the area of a spinal cord injury.

Future Based on the knowledge acquired from this study, scientists hope to use medicine to stop the “chain reaction” that occurs stemming from the effected Hsp90 protein. For example: researchers could produce a drug that a stroke patient could take at the beginning signs of their symptoms. Preventing healthy cells from dying and limiting the effects of the stroke. Since oxidation is also linked to inflammation, researchers believe this study could lead to discoveries to other problems including heart disease, cancer, aging, chronic pain, and other neurodegenerative conditions.

Sources University of Central Florida. "Discovery of 'executioner' protein opens door to new options for stroke ALS, spinal cord injury." ScienceDaily, 4 Mar Web. 1 Nov "New York State Spinal Cord Injury Center of Research Excellence." New York State Spinal Cord Injury Center of Research Excellence. N.p., n.d. Web. 01 Nov "What Is ALS?" - The ALS Association. N.p., n.d. Web. 02 Nov als/what-is-als.html "Spinal Injury." Wikipedia. Wikimedia Foundation, 29 Oct Web. 02 Nov "Hsp90." Wikipedia. Wikimedia Foundation, 15 Aug Web. 02 Nov "What Is Oxidative Stress?" What Is Oxidative Stress? N.p., n.d. Web. 02 Nov "Bioscience Technology." Bioscience Technology. N.p., n.d. Web. 02 Nov "What Is Stroke?" What Is Stroke? N.p., n.d. Web. 04 Nov