X-Message-Number: 28724
Date: Wed, 6 Dec 2006 11:57:15 -0800 (PST)
Subject: fly longevity experiment wish list

[If anybody is willing to donate a small sample of either memantine or
rapamycin for a fly longevity test please contact me privately. Fly
longevity is known to be limited by motor neuron degeneration, and these
prescription items may affect this.]

J Neural Transm Suppl. 2004;(68):117-22.
The N-methyl-D-aspartate antagonist memantine retards progression of
Huntington's disease.
  According to the excitotoxicity hypothesis, neurotoxicity due to
glutamate is regarded as potential factor in the progredient
neurodegeneration of Huntington's disease (HD). Memantine, as a glutamate
receptor antagonist, should counteract this mechanism. Its effectiveness
(up to 30 mg/day) with regard to retardation of progression was thus
examined in 27 HD patients in a two year, open and multicentre trial. The
results suggest that memantine treatment of HD may be useful in terms of
retardation of the progression of the disorder.

Mol Aspects Med. 2006 October - December;27(5-6):520-527. Epub 2006 Sep
Role of autophagy in the clearance of mutant huntingtin: A step towards
  Macroautophagy (henceforth referred to simply as autophagy) is a bulk
degradation process involved in the clearance of long-lived proteins,
protein complexes and organelles. A portion of the cytosol, with its
contents to be degraded, is enclosed by double-membrane structures called
autophagosomes/autophagic vacuoles, which ultimately fuse with lysosomes
where their contents are degraded. In this review, we will describe how
induction of autophagy is protective against toxic intracytosolic
aggregate-prone proteins that cause a range of neurodegenerative
diseases. Autophagy is a key clearance pathway involved in the removal of
such proteins, including mutant huntingtin (that causes Huntington's
disease), mutant ataxin-3 (that causes spinocerebellar ataxia type 3),
forms of tau that cause tauopathies, and forms of alpha-synuclein that
cause familial Parkinson's disease. Induction of autophagy enhances the
clearance of both soluble and aggregated forms of such proteins, and
protects against toxicity of a range of these mutations in cell and
animal models. Interestingly, the aggregates formed by mutant huntingtin
sequester and inactivate the mammalian target of rapamycin (mTOR), a key
negative regulator of autophagy. This results in induction of autophagy
in cells with these aggregates.

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