Huntington's accomplice captured?

While looking into the crime of Huntington's disease, investigators have nabbed a new suspect-a protein that plays a role in generating energy for cells. In 1993, researchers learned that this fatal neurodegenerative disorder results from unexplained genetic stutters, expansions in the size of a particular gene. The stutters add extra strings of the amino acid glutamine to huntingtin, the protein that the gene normally encodes. Several other genes stutter similarly, leading to neurodegenerative diseases that share characteristics with Huntington's.

In November 1995, researchers found a clue they hoped might reveal the normal function of huntingtin and how mutant versions of it cause Huntington's disease. They discovered a novel brain protein that binds more tightly to mutant huntingtin than to the normal form (SN: 11/18/95, p. 325). No one knows the protein's purpose in brain cells, however.

Now, investigators from Duke University Medical Center in Durham, N.C., and Stanford University School of Medicine have found another brain protein that hugs mutant huntingtins more tightly than normal versions. Equally important, this protein, called GAPDH, has a number of known functions, such as providing energy to cells, report Warren J. Strittmatter of Duke and his colleagues in the March Nature Medicine.

The investigators speculate that brain cell death in Huntington's disease may stem from cells being starved for energy because of inappropriate interactions between mutant huntingtins and GAPDH. Abnormal attachments to GAPDH may also explain other neurodegenerative disorders caused by genetic stutters-the crucial proteins produced in at least two of those diseases also appear to bind to GAPDH.