HUNTINGTON DISEASE: TREAHALOSE ROLE
The disease, first
described by George Huntigton, is a result from a mutation in a gene called huntingtin
found on chromosome 4, which contains CAG triplet coding for glutamine
repeated dozens of times: polyglutamine-induced protein aggregation is the key
biochemical disorder.
Inhibition of
polyglutamine-induced protein aggregation could provide treatment options.
Motomasa Tanaka, Yoko Machida, Sanyong Niu, Tetsurou Ikeda, Nihar R Jana,
Hiroshi Doi, Masaru Kurosawa, Munenori Nekooki & Nobuyuki Nukina showed
through in vitro screening studies that various disaccharides can
inhibit polyglutamine-mediated protein aggregation (Trehalose alleviates polyglutamine-mediated pathology in a mouse model
of Huntington disease, Nature Medicine 10, 2, 148 – 154, February 2004). The authors also found
that various disaccharides reduced polyglutamine aggregates and increased
survival in a cellular model of Huntington disease. Oral administration of
trehalose, the most effective of these disaccharides, decreased polyglutamine
aggregates in cerebrum and liver, improved motor dysfunction and extended
lifespan in a transgenic mouse model of Huntington disease. They suggest that
these beneficial effects are the result of trehalose binding to expanded
polyglutamines and stabilizing the partially unfolded polyglutamine-containing
protein. Lack of toxicity and high solubility, coupled with efficacy upon oral
administration, make trehalose promising as a therapeutic drug or lead compound
for the treatment of polyglutamine diseases. The saccharide-polyglutamine
interaction identified in this work thus provides a new therapeutic strategy
for polyglutamine diseases.