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Trembling hands and molecular handshakes
Date:10/23/2009

Fragile X tremor/ataxia syndrome (FXTAS) is a recently recognized condition, which is actually one of the most prevalent heritable neurodegenerative diseases. It is assumed that the condition is caused by deficiency for the protein Pur-alpha, which is essential for normal neural function. Structural studies undertaken by a team under the leadership of Dr. Dierk Niessing of the Helmholtz Zentrum Mnchen and the Gene Center at Ludwigs-Maximilians-University (LMU) have now determined the three-dimensional structure of Pur-alpha, and gained insights into the molecular function of the protein. The findings provide a possible basis for the development of an effective therapy for the disease.(PNAS Early Edition, 21. Oktober 2009)

Most FXTAS patients are males, and symptoms of the condition become manifest around the age of 55. As the disease progresses, patients develop tremor in their hands and also show ataxia, i.e. they have difficulty maintaining their balance when they move, and therefore have a tendency to fall. Quite often these deficits are accompanied by cognitive defects and dementia.

The underlying cause of FXTAS is a mutation in the gene for FMRP (Fragile X Mental Retardation Protein). This mutation is found on the X chromosome in one out of 800 men, and involves abnormal expansions of a DNA sequence composed of repeats of the base triplet CGG. Healthy people have between 5 and 54 copies of this sequence, while those who will develop FXTAS are born with between 55 and 200 repeats. Expansion of the triplet sequence beyond 200 copies leads to Fragile X Syndrome (FXS), which is the second most common cause of hereditary mental retardation after Down's syndrome. FXTAS itself is apparently triggered by a lack of the protein Pur-alpha. This protein binds to the CGG sequences in FMR messenger RNAs (mRNA). The excessive numbers of CGG triplets found in the mutant FMRP mRNA essentially bind so much Pur-alpha that insufficient amounts are ava
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Contact: Dr. Dierk Niessing
niessing@lmb.uni-muenchen.de
49-892-180-76962
Ludwig-Maximilians-Universitt Mnchen
Source:Eurekalert

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