Inhibition of polyglutamine aggregation in R6/2 HD brain slices - Complex dose-response profiles

Donna L. Smith, Ruben Portier, Ben Woodman, Emma Hockly, Amarbirpal Mahal, William E. Klunk, Xiao Jiang Li, Erich Wanker, Karl D Murray, Gillian P. Bates

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Huntington's disease (HD) is a late onset neurodegenerative disorder caused by a CAG/polyglutamine (polyQ) repeat expansion. PolyQ aggregates can be detected in the nuclei and processes of neurons in HD patients and mouse models prior to the onset of symptoms. The misfolding and aggregation pathway is an important therapeutic target. To better test the efficacy of aggregation inhibitors, we have developed an organotypic slice culture system. We show here that the formation of polyQ aggregates in hippocampal slices established from the R6/2 mouse follows the same prescribed sequence as occurs in vivo. Using this assay, we show that Congo red and chrysamine G can modulate aggregate formation, but show complex dose-response curves. Oral administration of creatine has been shown to delay the onset of all aspects of the phenotype and neuropathology in R6/2 mice. We show here that creatine can similarly inhibit aggregate formation in the slice culture assay.

Original languageEnglish (US)
Pages (from-to)1017-1026
Number of pages10
JournalNeurobiology of Disease
Volume8
Issue number6
DOIs
StatePublished - 2001

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Huntington Disease
Creatine
Brain
Congo Red
Neurodegenerative Diseases
Oral Administration
Phenotype
Neurons
Inhibition (Psychology)
polyglutamine
Therapeutics

ASJC Scopus subject areas

  • Neurology

Cite this

Smith, D. L., Portier, R., Woodman, B., Hockly, E., Mahal, A., Klunk, W. E., ... Bates, G. P. (2001). Inhibition of polyglutamine aggregation in R6/2 HD brain slices - Complex dose-response profiles. Neurobiology of Disease, 8(6), 1017-1026. https://doi.org/10.1006/nbdi.2001.0438

Inhibition of polyglutamine aggregation in R6/2 HD brain slices - Complex dose-response profiles. / Smith, Donna L.; Portier, Ruben; Woodman, Ben; Hockly, Emma; Mahal, Amarbirpal; Klunk, William E.; Li, Xiao Jiang; Wanker, Erich; Murray, Karl D; Bates, Gillian P.

In: Neurobiology of Disease, Vol. 8, No. 6, 2001, p. 1017-1026.

Research output: Contribution to journalArticle

Smith, DL, Portier, R, Woodman, B, Hockly, E, Mahal, A, Klunk, WE, Li, XJ, Wanker, E, Murray, KD & Bates, GP 2001, 'Inhibition of polyglutamine aggregation in R6/2 HD brain slices - Complex dose-response profiles', Neurobiology of Disease, vol. 8, no. 6, pp. 1017-1026. https://doi.org/10.1006/nbdi.2001.0438
Smith, Donna L. ; Portier, Ruben ; Woodman, Ben ; Hockly, Emma ; Mahal, Amarbirpal ; Klunk, William E. ; Li, Xiao Jiang ; Wanker, Erich ; Murray, Karl D ; Bates, Gillian P. / Inhibition of polyglutamine aggregation in R6/2 HD brain slices - Complex dose-response profiles. In: Neurobiology of Disease. 2001 ; Vol. 8, No. 6. pp. 1017-1026.
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