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Neuroscience

Good and bad cell death

Nature volume 457, pages 970–971 (2009)Cite this article

Neurodegeneration often has disease connotations. However, it is also a developmental process for fine sculpting of the nervous system. One signalling cascade might mediate the process in both circumstances.

A major driver of neurodegeneration in Alzheimer's disease is thought to be plaques of amyloid-β peptides. These 40–42-amino-acid fragments form when the transmembrane amyloid-β precursor protein (APP) is degraded by the enzymes β- and γ-secretase. In addition to amyloid-β peptides, degradation of APP results in the formation of other peripheral fragments1. Perhaps unsurprisingly, given the compelling link between the deposition of amyloid-β peptides and the development of Alzheimer's disease2,3, these additional fragments have been outshone and have received scant attention. But on page 981 of this issue, Nikolaev and colleagues4 report that one oft-neglected fragment — the soluble amino-terminal portion of APP (N-APP) — has a crucial role in fine-sculpting of the nervous system during development, and possibly in disease-associated neurodegeneration as well.

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Figure 1: Neurodegeneration signalling cascade.

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  1. Donald W. Nicholson is at Merck Research Laboratories, Rahway, New Jersey 07065, USA. donald_nicholson@merck.com ,

    Donald W. Nicholson

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  1. Donald W. Nicholson
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Nicholson, D. Good and bad cell death. Nature 457, 970–971 (2009). https://doi.org/10.1038/457970a

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