« 3,000 Brains | Main | Nancy Wexler »
June 16, 2004
Alzheimer's Polyglutamine Connection
Huntington's Disease is a 'polyglutamine' disease. That is, the DNA codes a string of glutamine that is too long in the gene responsible for the huntingtin protein.
Researchers have found that in Alzheimer's there is a string of glutamine that is too long in an important transcription factor - TATA binding protein (TBP). It's possible (though far from probable at this point) that down the road the gene therapy work being done for HD may lead to a cure for Alzheimers.
Perhaps this finding will cause more money to be poured into polyglutamine research. Here is the study abstract (hat tip to Malcolm C. for pointing this article out):
Brain Res Mol Brain Res. 2004 Jun 18;125(1-2):120-8.
TBP, a polyglutamine tract containing protein, accumulates in Alzheimer's disease.
Reid SJ, Van Roon-Mom WM, Wood PC, Rees MI, Owen MJ, Faull RL, Dragunow M, Snell RG. Department of Pharmacology, University of Auckland, Auckland, New Zealand.
Alzheimer's disease (AD) is characterised by extra cellular beta-amyloid (betaA) deposition, Tau-containing neurofibrillary tangles (NFTs) and progressive cortical atrophy. Abnormal protein accumulation is also a common feature of other late onset neurodegenerative diseases, including the heritable polyglutamine (polyQ) disorders such as Huntington disease (HD) and the spinocerebellar ataxias (SCAs). One of this family of disorders, SCA17, is caused by an expansion of a polymorphic polyQ repeat in TATA binding protein (TBP), an essential transcription factor. Surprisingly, the wild type TBP repeat length ranges from 25 to 42, and in Caucasian populations the most common allele is 38, a size large enough to cause HD if within the huntingtin protein. Wild type length TBP accumulates in HD and in at least some of the SCAs, and consequently we hypothesised that it may contribute to AD. Here we provide evidence that TBP accumulates in AD brain, localising to neurofibrillary tangle structures. A proportion of TBP present in AD brain is insoluble; a signature of the polyQ diseases. TBP is present differentially between patients and its amount and distribution is not directly proportional to that of Tau or beta-amyloid positive structures. We present this as evidence for the hypothesis that the accumulation or misfolding of this polyQ containing protein may be a contributing factor in Alzheimer's disease.
Posted by Dave at June 16, 2004 09:29 PM
Trackback Pings
TrackBack URL for this entry:
http://www.huntingtons.info/MT/mt-tb.cgi/469
Comments
Post a comment
Thanks for signing in, . Now you can comment. (sign out)
(If you haven't left a comment here before, you may need to be approved by the site owner before your comment will appear. Until then, it won't appear on the entry. Thanks for waiting.)