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“A third of the adults and half of the children with AIDS develop HIV-1-associated dementia,” explains Dr. Nuran Ercal, professor of chemistry at UMR and adjunct associate professor of internal medicine at Saint Louis University. “Cognitive impairment, postural disorders and tremors are among the most common symptoms encountered in patients suffering from AIDS dementia complex.”
Ercal collaborated with Dr. William Banks, professor of geriatric medicine at Saint Louis University, to determine whether the antioxidant N-acetylcysteine amide (NACA) could prevent cell death and reverse oxidative stress, a condition associated with many different irreversible neurological degeneration diseases, including Parkinson’s and Alzheimer’s.
“There’s a beautiful balance in our bodies,” Ercal says. “We have these free radicals -- atoms and molecules with an unpaired electron that attack other molecules. Our bodies have developed a natural antioxidant defense system that includes enzymes and small molecules to overcome harmful effects of these attacks. If the balance is tipped over, then we have oxidative stress.”
The researchers narrowed their study to the blood-brain barrier, a selective barrier that controls the entry of substances from the blood into the brain. They believed two toxic HIV proteins -- the envelope glycoprotein (gp120) and transregulatory protein (Tat) -- could be disrupting the protective barrier and allowing toxic materials to pass through to the brain. If true, the proteins could be inducing oxidative stress in the cells and causing dementia in patients.
Using an artificial model of a rat’s blood-brain barrier, the researchers incubated cells with the viral proteins for 24 hours. Every parameter the researchers then employed to measure oxidative stress described the same scenario: both gp120 and Tat were inducing oxidative stress in the rat brain capillaries.
In previous studies involving lead poisoning and radiation exposure, Ercal had successfully used the originally formulated N-acetylcysteine (NAC), the drug of choice in treating acetaminophen overdoses, to combat the resulting oxidative stress. Unlike NAC, the newly synthesized NACA passes easily through cell membranes, leading researchers to believe NACA could reverse the oxidative stress levels in the blood-brain barrier.
“We found NACA, this new compound, prevented cell death,” Ercal adds. “NACA returned all parameters to their control levels, and it’s not harmful except in extremely high concentrations. Therefore, we determined that while treating AIDS patients, perhaps we should include antioxidants to prevent oxidative stress or prevent possible dementia.”
The researchers are now studying the brain and liver samples from transgenic rats. The animals have been genetically modified to contain gp120, allowing the researchers to further study the effects of this protein.
“If gp120 is causing these free radicals, then we should have lots of free radicals in these animals because they are continuously making this protein,” Ercal adds.