Neuroprotective signaling by hydrogen sulfide and its dysregulation in Alzheimer's disease

The ancient messenger molecule hydrogen sulfide (H₂S) modulates myriad signaling cascades and has been conserved across evolutionary boundaries. Although traditionally known as an environmental toxin, H₂S is also synthesized endogenously to exert modulatory and homeostatic effects in a broad array of physiologic functions. Notably, H₂S levels are tightly physiologically regulated, as both its excess and paucity can be toxic. Accumulating evidence has revealed pivotal roles for H₂S in neuroprotection and normal cognitive function, and H₂S homeostasis is dysregulated in neurodegenerative conditions. Here, we review the normal neuroprotective roles of H₂S that go awry in Alzheimer's disease, the most common form of neurodegenerative disease.