Sirtuins Contribute to the Migraine-Stroke Connection.

The prevalence of stroke in patients with migraine is higher than in the general population, suggesting certain shared mechanisms of pathogenesis. Migrainous infarction is a pronounced example of the migraine-stroke connection. Some cases of migraine with aura may be misdiagnosed as stroke, with subsequent mistreatment. Therefore, it is important to identify these shared mechanisms of pathogenesis contributing to the migraine-stroke connection to improve diagnosis and treatment. Sirtuins (SIRTs) are a seven-member family of NAD-dependent histone deacetylases that can epigenetically regulate gene expression. Sirtuins possess antioxidant properties, making them a first-line defense against oxidative stress, which is important in the pathogenesis of migraine and stroke. Mitochondrial localization of SIRT2, SIRT3, and SIRT4 supports this function, as most reactive oxygen and nitrogen species are produced in mitochondria. In this narrative review, we present arguments that sirtuins may link migraine with stroke through their involvement in antioxidant defense, mitochondrial quality control, neuroinflammation, and autophagy. We also indicate mediators of this involvement that can be, along with sirtuins, therapeutic targets to ameliorate migraine and prevent stroke.