Strategies for gaseous neuromodulator release in chemical neuroscience: Experimental approaches and translational validation

Gasotransmitters are a group of short-lived gaseous signaling molecules displaying diverse biological functions depending upon their localized concentration. Nitric oxide (NO), hydrogen sulfide (H2S), and carbon monoxide (CO) are three important examples of endogenously produced gasotransmitters that play a crucial role in human neurophysiology and pathogenesis. Alterations in their optimal physiological concentrations can lead to various severe pathophysiological consequences, including neurological disorders. Exogenous administration of gasotransmitters has emerged as a prominent therapeutic approach for treating such neurological diseases. However, their gaseous nature and short half-life limit their therapeutic delivery. Therefore, developing synthetic gasotransmitter-releasing strategies having control over the release and duration of these gaseous molecules has become imperative. However, the complex chemistry of synthesis and the challenges of specific quantified delivery of these gases, make their therapeutic application a challenging task. This review article provides a focused overview of emerging strategies for delivering gasotransmitters in a controlled and sustained manner to re-establish neurophysiological homeostasis.