Scientists at Scripps Research in California have found an important immune system-regulating protein that in principle could be targeted to treat cancers and chronic viral infections. In a study published online on November 12, 2018 in Nature Chemical Biology, the scientists set out to determine the function of a protein, ABHD12 (abhydrolase domain containing protein 12), whose absence causes a rare genetic disease featuring a host of brain and nerve problems. The article is titled “Selective Blockade of the Lyso-PS Lipase ABHD12 Stimulates Immune Responses in Vivo.” The researchers found that ABHD12 normally acts as a powerful "brake" on the immune system to keep it from becoming harmfully overactive. Mice engineered without the protein have signs of elevated inflammation, and their immune systems are more likely to overreact to a viral infection. The discovery suggests that the absence of ABHD12 in people with mutant versions of its gene may cause neurological disease at least in part via excessive immune activity. It also indicates that ABHD12 may be a useful target for drugs that boost the immune system--for example against cancers and viruses that normally persist by shutting down people's immune defenses. "This is a good example of how the study of a rare genetic disease can reveal a pathway that plays a key role in human biology," says study co-senior author Benjamin Cravatt, PhD, Professor and Chair of the Department of Chemical Physiology at Scripps Research. The rare disease in this case is a mix of progressive brain, peripheral nerve, and eye problems that scientists have given the acronym PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract). Since 2010, researchers have known that PHARC is caused by gene mutations that prevent ABHD12 from being made.
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