Worm Studies Illuminate Biology of Huntington’s Disease

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Proteins are key to almost everything cells do, but in order to function, they must fold into the right shape. Luckily, folding mistakes are rare. When they occur, cells have ways to fix them, as well as to recycle proteins that are beyond repair. If these measures fail, misshapen proteins can accumulate into clumps that damage and destroy cells. Such clumps are common in Huntington’s disease. Two recent studies, both done in roundworms, provide clues about how early cell damage quickly spreads and potentially contributes to the development of this neurological condition. Roundworms are easily studied and share many traits with other organisms, including humans, making them an ideal model for examining biological processes.

In one investigation, biochemist Richard Morimoto, Ph.D., of Northwestern University in Evanston, Illinois, discovered that misshapen Huntington's disease proteins skirt normal repair mechanisms. He suspects that the culprit is a telltale protein shape that assails otherwise normal protein neighbors, causing them to unravel and form massive clumps. This disruption of the cell's internal equilibrium, in turn, spurs a cascade of damaging events.

In a separate study, Mervyn Monteiro, Ph.D., of the University of Maryland Biotechnology Institute in Baltimore identified a helpful protein, called ubiquilin. He discovered that when ubiquilin is abundant in worm cells, it suppresses the clumping of Huntington's disease proteins.

In addition to improving understanding of Huntington's disease, these results could shed light on the mechanisms underlying other neurological conditions—such as Parkinson's and Alzheimer's—that have been linked to protein clumping errors. The findings may also point the way to new targets for drugs to treat such disorders.