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Neurodegenerative diseases

Allies in the fight against neurodegeneration

Nature Reviews Neuroscience volume 5, page 896 (2004)Cite this article

Finkbeiner and colleagues developed an ingenious robotic microscope imaging system that can follow the survival of individual neurons, intracellular levels of mutant HTT and the formation of inclusion bodies in the same cells over several days to help them to understand changes in the risk of cell death that occur over time.

The results showed that neuronal death was related to the length of polyQ expansions in HTT. This effect remained constant over time and was therefore not related to an increase in the size or number of inclusion bodies over the same time period, nor was it related to the formation of inclusion bodies. Instead, it seems that polyQ expansion causes toxicity in more diffuse forms of HTT, independent of its effect on levels of intracellular HTT, and this triggers an increased risk of cell death. Higher levels of this toxic diffuse HTT were associated with earlier formation of inclusion bodies.

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References

ORIGINAL RESEARCH PAPER

  1. Arrasate, M., Mitra, S., Schweitzer, E. S., Segal, M. R. & Finkbeiner, S. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 431, 805–810 (2004)

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FURTHER READING

  1. Orr, H. T. Neuron protection agency. Nature 431, 747–748 (2004)

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Authors
  1. Alison Rowan
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Rowan, A. Allies in the fight against neurodegeneration. Nat Rev Neurosci 5, 896 (2004). https://doi.org/10.1038/nrn1571

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