Trehalose opens new approach to treatment of polyglutamine diseases
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Huntington's disease (HD) is a progressive neurodegenerative disorder
caused by a mutation that expands the CAG polyglutamine repeat in the
huntingtin gene beyond normal. As the formation of insoluble protein
aggregates may be linked to the cellular distortions underlying HD,
molecules or proteins that inhibit their formation have been
investigated at RIKEN. In vitro screening studies showed that various
disaccharides can inhibit polyglutamine-mediated protein aggregation.
The most potent compound, trehalose, stabilized proteins containing an
expanded polyglutamine and decreased formation of aggregates dose-
dependently without inducing any cellular toxicity. Oral
administration (2%) in the R6/2 transgenic mouse model of HD decreased
polyglutamine aggregates in the cerebrum and liver, improved motor
dysfunction and extended life-span in a dose-dependent manner. The
elevated rate of diabetes in R6/2 mice mimics symptoms observed in HD
patients. The examination of fasting blood glucose in R6/2 and wild-
type trehalose-treated (2%) mice were comparable to that of control
mice. The interaction between disaccharide compounds and polyglutamine-
mediated protein aggregation may provide a novel approach for the
treatment of polyglutamine diseases (Tanaka, M. et al. Nat Med 2004,
10(2): 148).

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http://en.wikipedia.org/wiki/Trehalose

It is particularly effective when combined with phosphate ions[2].
Trehalose has also been used in at least one biopharmaceutical
formulation, the monoclonal antibody trastuzumab, marketed as
Herceptin.
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PROPERTIES OF TREHALOSETrehalose is a disaccharide composed of two
glucose molecules bound by an alpha, alpha-1, 1 linkage.Since the
reducing end of a glucosyl residue is connected with the other,
trehalose has no reducingpower. Trehalose is widely distributed in
nature. It is known to be one of the sources of energy in mostliving
organisms and can be found in many organisms, including bacteria,
fungi, insects, plants, andinvertebrates. Mushrooms contain up to 10-
25 % trehalose by dry weight. Furthermore, trehalose pro-tects
organisms against various stresses, such as dryness, freezing, and
osmopressure. In the case of res-urrection plants, which can live in a
dry state, when the water dries up, the plants dry up too.
However,they can successfully revive when placed in water. The
anhydrobitic organisms are able to tolerate thelack of water owing to
their ability to synthesize large quantities of trehalose, and the
trehalose plays akey role in stabilizing membranes and other
macromolecular assemblies under extreme environmentalconditions.The
properties of trehalose are shown in Table 1. Its relative sweetness
is 45 % of sucrose.Trehalose has high thermostability and a wide pH-
stability range. Therefore, it is one of the most sta-ble saccharides.
When 4 % trehalose solutions with 3.5 to 10 pH were heated at 100 °C
for 24 h, nodegradation of trehalose was observed in any case. Because
of nonreducing sugar, this saccharidedoes not show Maillard reaction
with amino compounds such as amino acids or proteins. Its partic-ular
physical features make it an extremely attractive substance for
industrial applications.Furthermore, this saccharide shows good
sweetness like sucrose, and in the food industry, this sac-charide is
used as a sweetener.*Pure Appl. Chem. Vol. 74, No. 7, 2002. A special
topic issue on the science of sweeteners.
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