Scientists from the University of Leicester and the University of Maryland have reversed Alzheimer’s and Parkinson’s symptoms by inhibiting an enzyme in fruit fly models, highlighting a new avenue to treat neurodegenerative diseases.
Maryland’s Robert Schwarcz and Leicester’s Flaviano Giorgini studied the amino acid tryptophan, which degrades in the body into several metabolites that have different effects on the nervous system. These include 3-hydroxykynurenine (3-HK), which can damage the nervous system, and kynurenic acid (KYNA), which can prevent nerve degeneration. The relative abundance of these two compounds in the brain could be critical in Parkinson’s, Alzheimer’s and Huntington’s disease, the University of Maryland said in a statement.
3-HK and KYNA exist in a balance between “good” and “bad” metabolites in the body. In neurodegenerative disease, the balance shifts toward the “bad,” Giorgini said in a statement. The researchers shifted the balance back toward “good” by giving genetically modified fruit flies a chemical that selectively inhibits the enzyme TDO, which controls the relationship between 3-HK and KYNA. This increased levels of the “protective” KYNA, and improved movement and lengthened life span in fruit flies genetically modified to model neurodegenerative disease.
Giorgini’s team at Leicester has previously used genetic approaches to inhibit TDO and another enzyme, KMO. The treatment lowered the levels of toxic tryptophan metabolites and reduced neuron loss in fruit fly models of Huntington’s disease.
It is estimated that 5 million Americans have Alzheimer’s disease and as many as 1 million have Parkinson’s. Current treatments may help to control symptoms but do not halt or delay disease progression. “Our hope is that by improving our knowledge of how these nerve cells become sick and die in the brain, we can help devise ways to interfere with these processes, and thereby either delay disease onset or prevent disease altogether,” Giorgini said in the Leicester statement. Giorgini's next step will be to validate the work in mammalian models.
Meanwhile, a UC San Diego team recently spotlighted the dendritic spines of neurons as a possible target in Alzheimer’s. And The Wall Street Journal reported this week that seniors are clamoring to participate in a clinical trial to see if the diabetes drug metformin can stave off the diseases that come with aging, including cognitive decline.
Image of Flaviano Giorgini courtesy of the University of Leicester.