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Insoluble TATA-binding protein accumulation in Huntington's disease cortex

van Roon-Mom, Willeke M.C, Reid, Suzanne J, Jones, Lesley ORCID: https://orcid.org/0000-0002-3007-4612, MacDonald, Marcy E, Faull, Richard L.M and Snell, Russell G 2002. Insoluble TATA-binding protein accumulation in Huntington's disease cortex. Molecular Brain Research 109 (1-2) , pp. 1-10. 10.1016/S0169-328X(02)00450-3

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Abstract

Huntington's disease is a dominantly inherited neurological disorder where specific neurodegeneration is caused by an extended polyglutamine stretch in the huntingtin protein. Proteins with expanded polyglutamine regions have the ability to self-aggregate and previous work in our laboratory, and by others, revealed sparse amyloid-like deposits in the Huntington's disease brain, supporting the hypothesis that the polyglutamine stretches may fold into regular P-sheet structures. This process of folding has similarities to other neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, and the prion diseases which all exhibit P-sheet protein accumulation. We were therefore interested in testing the hypothesis that TATA-binding protein may play a role in Huntington's disease as it contains an elongated polymorphic polyglutamine stretch that ranges in size from 26 to 42 amino acids in normal individuals. A proportion of TBP alleles fall within the range of glutamine length that causes neurodegeneration when located in the huntingtin protein. In this study the distribution and cellular localisation of TATA-binding protein was compared to the distribution and cellular localisation of the huntingtin protein in the middle frontal gyrus of Huntington's disease and neurologically normal subjects. Seven different morphological forms of TATA-binding protein-positive structures were detected in Huntington's disease but not in control brain. TATA-binding protein labelling was relatively more abundant than huntingtin labelling and increased with the grade of the disease. At least a proportion of this accumulated TBP exists as insoluble protein. This suggests that TBP may play a role in the disease process.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: Elsevier
ISSN: 0169-328X
Last Modified: 04 Mar 2023 03:03
URI: https://orca.cardiff.ac.uk/id/eprint/82906

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