Brain, Learning, and Memory: Role of H2S in Neurodegenerative Diseases.

For more than 300 years, the toxicity of hydrogen sulfide (H2S) has been known to mankind. However, this point of view is changing as an increased interest was observed in H2S biology in the last two decades. The scientific community has succeeded to unravel many important physiological and pathological effects of H2S on mammalian body systems. Thus, H2S is now referred to as a third endogenous gaseous mediator along with nitric oxide and carbon monoxide. Acting as a neuromodulator, H2S facilitates long-term potentiation and regulates intracellular calcium levels, which are important processes in learning and memory. Aberrant endogenous production and metabolism of H2S are implicated in pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD). Various H2S donors have shown beneficial therapeutic effects in neurodegenerative disease models by targeting hallmark pathological events (e.g., amyloid-β production in AD and neuroinflammation in PD). The results obtained from many in vivo studies clearly show that H2S not only prevents neuronal and synaptic deterioration but also improves deficits in memory, cognition, and learning. The anti-inflammatory, antioxidant, and anti-apoptotic effects of H2S underlie its neuroprotective properties. In this chapter, we will overview the current understanding of H2S in context of neurodegenerative diseases, with special emphasis on its corrective effects on impaired learning, memory, and cognition.