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Neurodegenerative disease

Searching for the weak spots

Nature Reviews Drug Discovery volume 13, pages 256–257 (2014)Cite this article

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In both mouse models and humans, ALS-associated neuronal death is selective for motor neurons that control voluntary movement. Of these, fast motor neurons are more prone to early loss than are slow motor neurons or oculomotor neurons. The authors compared microarray gene expression profiles in motor neuron subsets from wild-type mice and found that the expression of MMP9 was high in fast motor neurons but absent from slow and oculomotor neurons. No change in expression pattern was seen in SOD1G93A mice before the development of ALS symptoms; however, no MMP9-positive motor neurons remained in SOD1G93A mice with end-stage disease, which indicates that MMP9 may be a determinant of neurodegeneration.

Even when administered after the onset of muscle denervation, the inhibitor conferred some protection against fast motor neuron degeneration

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References

  1. Kaplan, A. et al. Neuronal matrix metalloproteinase-9 is a determinant of selective neurodegeneration. Neuron 81, 333–348 (2014)

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  1. Natasha Bray
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Bray, N. Searching for the weak spots. Nat Rev Drug Discov 13, 256–257 (2014). https://doi.org/10.1038/nrd4284

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