HUNTINGTON AND DRPLA PROTEINS SELECTIVELY INTERACT WITH THE ENZYME GAPDH

At least five adult-onset neurodegenerative diseases, including Huntin gton disease (HD), and dentatorubral-pallidoluysian atrophy (DRPLA) ar e produced by genes containing a variably increased CAG repeat within the coding region(1-4). The size range of the repeats is similar in al l diseases; unaffected individuals have fewer than 30 CAG repeats, whe reas affected patients usually have more than 40 repeats. The size of the inherited CAG repeat correlates with the severity and age of disea se onset(1,5-7). The CAG triplet repeat produces a polyglutamine domai n in the expressed proteins(3,8-10). All of these diseases are inherit ed in a dominant fashion, and a pathologic gain of function in gene ca rriers has been proposed. We sought to identify proteins in the brain that selectively interact with polyglutamine domain proteins, hypothes izing that the polyglutamine domain may determine protein-protein inte ractions.