Hydrogen sulfide (H₂S), a toxic gaseous molecule, plays a physiological role in regulating homeostasis and cell signaling. H₂S is produced from cysteine by enzymes, such as cystathionineβ‐synthase (CBS), cystathionineγ‐lyase (CSE), cysteine aminotransferase (CAT), and 3‐mercaptopyruvate sulfurtransferase (3MST). These enzymes regulate the overall production of H₂S in the body. H₂S has a cell‐signaling function in the CNS and plays important roles in combating oxidative species such as reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the body. H₂S is crucial for maintaining balanced amounts of antioxidants to protect the body from oxidative stress, and appropriate amounts of H₂S are required to protect the CNS in particular. The body regulates CBS, 3MST, and CSE levels in the CNS, and higher or lower levels of these enzymes cause various neurodegenerative diseases. This review discusses how H₂S protects the CNS by acting as an antioxidant that reduces excessive amounts of ROS and RNS. Additionally, H₂S regulates cell signaling to combat neuroinflammation and protect against central neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS).

Neuronal inflammation is a systematically organized physiological step often triggered to counteract an invading pathogen or to rid the body of damaged and/or dead cellular debris. At the crux of this inflammatory response is the deployment of nonneuronal cells: microglia, astrocytes, and blood‐derived macrophages. Glial cells secrete a host of bioactive molecules, which include proinflammatory factors and nitric oxide (NO). From immunomodulation to neuromodulation, NO is a renowned modulator of vast physiological systems. It essentially mediates these physiological effects by interacting with cyclic GMP (cGMP) leading to the regulation of intracellular calcium ions. NO regulates the release of proinflammatory molecules, interacts with ROS leading to the formation of reactive nitrogen species (RNS), and targets vital organelles such as mitochondria, ultimately causing cellular death, a hallmark of many neurodegenerative diseases. AD is an enervating neurodegenerative disorder with an obscure etiology. Because of accumulating experimental data continually highlighting the role of NO in neuroinflammation and AD progression, we explore the most recent data to highlight in detail newly investigated molecular mechanisms in which NO becomes relevant in neuronal inflammation and oxidative stress‐associated neurodegeneration in the CNS as well as lay down up‐to‐date knowledge regarding therapeutic approaches targeting NO.

Hydrogen sulfide (H₂S) is an emerging neuromodulator that is considered to be a gasotransmitter similar to nitrogen oxide (NO) and carbon monoxide (CO). H₂S exerts universal cytoprotective effects and acts as a defense mechanism in organisms ranging from bacteria to mammals. It is produced by the enzymes cystathionine β‐synthase (CBS), cystathionine ϒ‐lyase (CSE), 3‐mercaptopyruvate sulfurtransferase (MST), and D‐amino acid oxidase (DAO), which are also involved in tissue‐specific biochemical pathways for H₂S production in the human body. H₂S exerts a wide range of pathological and physiological functions in the human body, from endocrine system and cellular longevity to hepatic protection and kidney function. Previous studies have shown that H₂S plays important roles in peripheral nerve regeneration and degeneration and has significant value during Schwann cell dedifferentiation and proliferation but it is also associated with axonal degradation and the remyelination of Schwann cells. To date, physiological and toxic levels of H₂S in the human body remain unclear and most of the mechanisms of action underlying the effects of H₂S have yet to be fully elucidated. The primary purpose of this review was to provide an overview of the role of H₂S in the human body and to describe its beneficial effects.

To date, three main gasotransmitters, that is, hydrogen sulfide (H₂S), carbon monoxide (CO), and nitric oxide (NO), have been discovered to play major bodily physiological roles. These gasotransmitters have multiple functional roles in the body including physiologic and pathologic functions with respect to the cellular or tissue quantities of these gases. Gasotransmitters were originally known to have only detrimental and noxious effects in the body but that notion has much changed with years; vast studies demonstrated that these gasotransmitters are precisely involved in the normal physiological functioning of the body. From neuromodulation, oxidative stress subjugation, and cardiovascular tone regulation to immunomodulation, these gases perform critical roles, which, should they deviate from the norm, can trigger the genesis of a number of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The purpose of this review is to discuss at great length physical and chemical properties and physiological actions of H₂S, NO, and CO as well as shedding light on recently researched molecular targets. We particularly put emphasis on the roles in neuronal inflammation and neurodegeneration and neuronal repair.

Hydrogen sulfide (H₂S) is a gasotransmitter that acts as an antioxidant and exhibits a wide variety of cytoprotective and physiological functions in age-associated diseases. One of the major causes of age-related diseases is oxidative stress. In recent years, the importance of H₂S has become clear, although its antioxidant function has not yet been fully explored. The enzymes cystathionine β-synthase, cystathionine γ-lya-se, and 3-mercaptopyruvate sulfurtransferase are involved in the enzymatic production of H₂S. Previously, H₂S was considered a neuromodulator, given its role in long-term hippocampal potentiation, but it is now also recognized as an antioxidant in age-related neurodegeneration. Due to aerobic metabolism, the central nervous system is vulnerable to oxidative stress in brain aging, resulting in age-associated degenerative diseases. H₂S exerts its antioxidant effect by limiting free radical reactions through the activation of antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, which protect against the effects of aging by regulating apoptosis-related genes, including p53, Bax, and Bcl-2. This review explores the implications and mechanisms of H₂S as an antioxidant in age-associated neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and Down syndrome.