FIGURE 2.2. Model for polyglutamine-expanded huntingtin transcription interference of BDNF gene expression.

FIGURE 2.2

Model for polyglutamine-expanded huntingtin transcription interference of BDNF gene expression. Promoters containing a neuron-restrictive silencing element (a) are bound by transcription repressors that prevent expression of downstream genes, such as BDNF, in non-neural cell types. In normal neurons (b), normal huntingtin protein is localized to the cytosol and binds the transcription repressor REST there, allowing BDNF gene expression to occur. However, in HD neurons (c), polyglutamine-expanded huntingtin protein accumulates in the nucleus and does not sequester REST in the cytosol. REST thus inappropriately enters neuronal nuclei and represses neuronal expression of BDNF in HD. (From Thompson, L. M., Nat Genet 35, 13, 2003. With permission.)

From: Chapter 2, Huntington’s Disease Pathogenesis

Cover of Neurobiology of Huntington's Disease
Neurobiology of Huntington's Disease: Applications to Drug Discovery.
Lo DC, Hughes RE, editors.
Boca Raton (FL): CRC Press; 2011.
Copyright © 2011 by Taylor and Francis Group, LLC.

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