Researchers at Case Western Reserve University have identified a cholesterol-processing enzyme that could protect against brain lesions in neurologic disorders. Photo by Volt Collection/Shutterstock
March 1 (UPI) -- Researchers from Case Western Reserve University School of Medicine have found an enzyme in the brain that could reduce the formation of debilitating brain lesions in neurological diseases.
The enzyme's primary purpose is to eliminate excess cholesterol from the brain and was found to remove the cholesterol-like molecule cholestanol.
Cholestanol is generally found in low levels but is significantly elevated in people with the rare, incurable genetic disease cerebrotendinous xanthomatosis.
"We found that an enzyme called CYP46A1 not only eliminates cholesterol but also cholestanol from the brain," Dr. Irina Pikuleva, vice chair of research in the Department of Ophthalmology and Visual Sciences at Case Western Reserve University School of Medicine, said in a press release. "CYP46A1 also seems to eliminate cholestanol from many regions of the brain except the cerebellum."
People with cerebrotendinous xanthomatosis have toxic levels of cholestanol in their cerebellums.
"Cholestanol accumulation in the body reflects an imbalance between its production and its elimination," Pikuleva said. "We found there are differences in the way brain regions eliminate cholesterol and cholestanol."
Researchers used mice that were genetically engineered to lack the enzymes involved in the process to determine how cholestanol is eliminated. The mice metabolized brain cholestanol at different rates in different regions of the brain, depending on the ratios of cholesterol and cholestanol-processing enzymes present.
Harmful accumulations of cholestanol could be removed by enhancing the activity of CYP46A1 in the brain pharmacologically through drugs already approved by the FDA, such as the HIV medication efavirenz.
"If successful, this trial will identify CYP46A1 as a new pharmacologic target not only for the treatment of people with mild cognitive impairment due to early stage Alzheimer's disease, but also for patients with cerebrotendinous xanthomatosis who do not respond to standard treatment," Pikuleva said.
The study was published in the Journal of Biological Chemistry.