Protective Roles of Hydrogen Sulfide in Alzheimer’s Disease and Traumatic Brain Injury

The gaseous signaling molecule hydrogen sulfide (H(2)S) critically modulates a plethora of physiological processes across evolutionary boundaries. These include responses to stress and other neuromodulatory effects that are typically dysregulated in aging, disease, and injury. H(2)S has a particularly prominent role in modulating neuronal health and survival under both normal and pathologic conditions. Although toxic and even fatal at very high concentrations, emerging evidence has also revealed a pronounced neuroprotective role for lower doses of endogenously generated or exogenously administered H(2)S. Unlike traditional neurotransmitters, H(2)S is a gas and, therefore, is unable to be stored in vesicles for targeted delivery. Instead, it exerts its physiologic effects through the persulfidation/sulfhydration of target proteins on reactive cysteine residues. Here, we review the latest discoveries on the neuroprotective roles of H(2)S in Alzheimer’s disease (AD) and traumatic brain injury, which is one the greatest risk factors for AD.