NO and neuronal cell death

Matrix metalloproteinases (MMPs) play a part in the pathogenesis of neurodegenerative disorders and stroke, but the mechanism behind MMP activation has been unclear. In 16 August Science, Zezong Gu and colleagues at The Burnham Institute, La Jolla, US, show that nitric oxide (NO) activates MMP-9 (which is particularly elevated in stroke) and leads to neuronal apoptosis (Science 2002, 297:1186-1190).

Gu et al. affinity-precipitated MMP-9 from rat brain following a two-hour focal cerebral ischaemia or from the contralateral (control) region of the brain. They performed mass spectrophotometry on tryptic fragments of the MMP-9 and observed that in ischaemic tissue, MMP-9 activation by NO resulted in S-nitrosylation and the generation of stable sulfinic or sulfonic acid active derivatives — both in vitro and in vivo. The MMP enzymes were further affected by other reactive oxygen species that led to their permanent pathological activity, causing them to attack the extracellular matrix of neurons ...