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).

Mitophagy is activated by a number of stimuli, including hypoxia, energy stress, and increased oxidative phosphorylation activity. Mitophagy is associated with oxidative stress conditions and central neurodegenerative diseases. Proper regulation of mitophagy is crucial for maintaining homeostasis; conversely, inadequate removal of mitochondria through mitophagy leads to the generation of oxidative species, including reactive oxygen species and reactive nitrogen species, resulting in various neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. These diseases are most prevalent in older adults whose bodies fail to maintain proper mitophagic functions to combat oxidative species. As mitophagy is essential for normal body function, by targeting mitophagic pathways we can improve these disease conditions. The search for effective remedies to treat these disease conditions is an ongoing process, which is why more studies are needed. Additionally, more relevant studies could help establish therapeutic conditions, which are currently in high demand. In this review, we discuss how mitophagy plays a significant role in homeostasis and how its dysregulation causes neurodegeneration. We also discuss how combating oxidative species and targeting mitophagy can help treat these neurodegenerative diseases.

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.

Jung J, et al. Int Neurourol J. 2012 Sep;16(3):102-106. http://dx.doi.org/10.5213/inj.2012.16.3.102

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.