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Neurodegeneration A silent channel opens its gates

Nature volume 388, pages 716–717 (1997)Cite this article

Many human neurodegenerative diseases, such as amyotrophic lateral sclerosis (also known as Lou Gehrig's disease), Alzheimer's disease, Parkinson's disease and Huntington's chorea, lead to the demise of distinct nerve-cell populations. Yet in no case is the selective vulnerability of the affected cells, nor the underlying damaging principle, understood.

A popular view is that these sinister diseases are caused – or at the very least exacerbated – by the unphysiological activity of cation-selective membrane channels operated by glutamate, which is the most abundant excitatory neurotransmitter in the brain. Now, the discovery by Zuo et al.1 (page 769of this issue) provides the first direct evidence in support of this view. The authors have traced the selective neurodegeneration that occurs in a spontaneous neurological mouse mutant (lurcher) to the constitutive activation of a member of the glutamate-receptor-channel family.

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Figure 1: Purkinje cells in the cerebellum express the glutamate receptor (GluR) δ2 subunit which, possibly together with an unknown subunit partner, forms a cation channel that is activated by glutamate or by a related excitatory transmitter.

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  1. Department of Molecular Neuroscience, Max Planck Institute for Medical Research, Jahnstrasse 29, D-69120, Heidelberg, Germany

    Peter H. Seeburg

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  1. Peter H. Seeburg
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Seeburg, P. Neurodegeneration A silent channel opens its gates. Nature 388, 716–717 (1997). https://doi.org/10.1038/41880

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