Neuronal cell death system with intranuclear and cytoplasmic polyglutamine aggregation

Japanese researchers have discovered that a simple sugar prevents neurodegeneration in a mouse model of the genetic disorder Huntington disease (HD).

Folk singer Woody Guthrie died of HD aged 55 in 1967.

According to Nobuyuki Nukina and colleagues at RIKEN Brain Science Institute, in Saitama, Japan, trehalose is non-toxic and can be administered orally. The investigators first discovered trehalose during experiments on a faulty protein involved in HD. The protein has a so-called "polyglutamine repeat", in which multiple copies of the amino acid glutamine are stacked together. This faulty protein forms aggregates in the brain which scientists believe cause the symptoms of HD.

The researchers found that mice with HD fed trehalose had fewer aggregates in their brains, better motor function, and lived longer. The benefits are not without limit, however. The compound prevents the formation of new aggregates but does not reverse the pathology.

The researchers suggest that trehalose may also have potential against other disorders caused by aggregation of proteins with polyglutamine repeats.

Nature Medicine, 2004, in press; http://dx.doi.org/10.1038/nm985