Noncanonical transnitrosylation network contributes to synapse loss in Alzheimer’s disease

We describe mechanistically-distinct enzymes, i.e., a kinase, a guanosine triphosphatase and a ubiquitin protein hydrolase, which function in disparate biochemical pathways, that can also act in concert to mediate a series of redox reactions. Each enzyme manifests a second, noncanonical function – transnitrosylation – triggering a pathological biochemical cascade in Alzheimer’s disease (AD). The resulting series of transnitrosylation reactions contributes to synapse loss, the major pathological correlate to cognitive decline in AD. We conclude that enzymes with distinct primary reaction mechanisms can form a completely separate network for aberrant transnitrosylation. This network operates in the post-reproductive period, so natural selection against such abnormal activity may be decreased.