Cause of neural death in neurodegenerative diseases attributable to expansion of glutamine repeats

Abstract

Neurodegenerative diseases resulting from expanded repeat sequences of glutamine residues are associated with the formation of protein aggregates in the cell nuclei of the affected neurons, but whether these are pathogenic is controversial. Recent observations indicate that the ages of onset of these diseases are exponential functions of the repeat lengths and that the probability of neural death is constant with time. The only process known to us that could give rise to such behaviour is nucleation of the aggregates.

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Figure 1: Aggregation from several nuclei of the exon-1 product of the Huntington's disease gene with a repeat of 47 glutamine residues, tagged with a fluorescent protein of relative molecular mass 26,000, and expressed in a single COS-1 cell.

Image courtesy of A. Kazantsev, E. Preisinger and D. Ho.

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Perutz, M., Windle, A. Cause of neural death in neurodegenerative diseases attributable to expansion of glutamine repeats. Nature 412, 143–144 (2001). https://doi.org/10.1038/35084141

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