Tying up loose ends | Nature Reviews Drug Discovery

Access through your institution Buy or subscribe It had been known that the nerve-cell damage that triggers their demise during stroke, Alzheimer's disease and other neurodegenerative

diseases not only occurs from inside the cell but externally too. The best-characterized nerve-cell-death pathways occur inside cells, but in terms of external mechanisms, two observations

had previously been made — levels of matrix metalloproteinases (particularly MMP9) are elevated in neurodegenerative disorders, and nitric oxide (NO) can modulate the activity of proteins

(in a manner that can be described as being analogous to phosphorylation) by reacting with cysteine thiols to form an _S_-nitrosylated derivative. Now, Lipton and colleagues show that these

two events are linked. They found that NO switches on the overexpression of MMP enzymes, which, in turn, chew up the environment that surrounds nerve cells. This is a preview of subscription

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ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES ORIGINAL RESEARCH PAPER * Lipton, S. A. et al. _S_-nitrosylation of

matrix metalloproteinases: signaling pathway to neuronal cell death. _Science_ 297, 1186–1190 (2002) Article  PubMed  Google Scholar  FURTHER READING * Yong, V. W., Power, C., Forsyth, P.

& Edwards, D. R. Metalloproteinases in biology and pathology of the nervous system. _Nature Rev. Neurosci._ 2, 502–511 (2001) Article  CAS  Google Scholar  Download references Authors *

Simon Frantz View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Frantz,

S. Tying up loose ends. _Nat Rev Drug Discov_ 1, 746 (2002). https://doi.org/10.1038/nrd931 Download citation * Issue Date: 01 October 2002 * DOI: https://doi.org/10.1038/nrd931 SHARE THIS

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