Pathophysiological functions of gas mediators in neurodegeneration

Abstract

Since the discovery of nitric oxide (NO) as gaseous signaling molecule, two other gaseous mediators, carbon monoxide (CO) and hydrogen sulfide (H₂S) have been found to be also involved in many physiological and pathophysiological functions. This review will briefly summarize our recent progress in the pathophysiology of NO and H₂S. In the photoreceptor cells, the level of intracellular Ca²⁺ is kept relatively low by H₂S. Intraperitoneal injection of H₂S donor to mice protected photoreceptor cells from light-induced retinal degeneration caused by oxidative stress and elevation of intracellular Ca²⁺. Another gaseous mediator NO induces Ca²⁺ release from the endoplasmic reticulum via S-nitrosylated type 1 ryanodine receptor (RyR1) Ca²⁺ release channel. NO-induced Ca²⁺ release (NICR) was abolished in primary cultured neurons from the knock-in mice, in which the S-nitrosylation site Cys-3636 of RyR1 was replaced by Ala (Ryr1^C3636A). The neurons in hippocampal CA3 region of Ryr1^C3636A mice were protected against seizure-induced neuronal cell death. The result indicates that NICR is critical for status epilepticus-induced neurodegeneration. The developments in the pathophysiology of gaseous mediators in the central nervous system will provide a better pharmacological advances for the treatment of neurodegenerative diseases.