Journal Article

Nebulized Glutathione as a Key Antioxidant for the Treatment of Oxidative Stress in Neurodegenerative Conditions

Lana, Jose Fábio, Rios, Alexandre, Santos, Napoliane, Pires, Luyddy, Takeyama, Renata, Santos, Gabriel Silva, Lana, João Vitor, Rodrigues, Izair Jefthé, Jeyaraman, Madhan, Purita, Joseph

2024

Overview

Glutathione (GSH), a tripeptide synthesized intracellularly, serves as a pivotal antioxidant, neutralizing reactive oxygen species (ROS) and reactive nitrogen species (RNS) while maintaining redox homeostasis and detoxifying xenobiotics. Its potent antioxidant properties, particularly attributed to the sulfhydryl group (-SH) in cysteine, are crucial for cellular health across various organelles. The glutathione-glutathione disulfide (GSH-GSSG) cycle is facilitated by enzymes like glutathione peroxidase (GPx) and glutathione reductase (GR), thus aiding in detoxification processes and mitigating oxidative damage and inflammation. Mitochondria, being primary sources of reactive oxygen species, benefit significantly from GSH, which regulates metal homeostasis and supports autophagy, apoptosis, and ferroptosis, playing a fundamental role in neuroprotection. The vulnerability of the brain to oxidative stress underscores the importance of GSH in neurological disorders and regenerative medicine. Nebulization of glutathione presents a novel and promising approach to delivering this antioxidant directly to the central nervous system (CNS), potentially enhancing its bioavailability and therapeutic efficacy. This method may offer significant advantages in mitigating neurodegeneration by enhancing nuclear factor erythroid 2-related factor 2 (NRF2) pathway signaling and mitochondrial function, thereby providing direct neuroprotection. By addressing oxidative stress and its detrimental effects on neuronal health, nebulized GSH could play a crucial role in managing and potentially ameliorating conditions such as Parkinson’s Disease (PD) and Alzheimer’s Disease (AD). Further clinical research is warranted to elucidate the therapeutic potential of nebulized GSH in preserving mitochondrial health, enhancing CNS function, and combating neurodegenerative conditions, aiming to improve outcomes for individuals affected by brain diseases characterized by oxidative stress and neuroinflammation.

• Publisher: MDPI AG
• Subject: Administration, Inhalation / Alzheimer's disease / Amino acids / Animals / Antioxidants / Antioxidants - administration & dosage / Antioxidants - pharmacology / Apoptosis / atomization / autophagy / bioavailability / biomedical research / Biosynthesis / brain / Care and treatment / Cysteine / Disease / disulfides / Endoplasmic reticulum / Enzymes / ferroptosis / Glutathione / Glutathione - administration & dosage / Glutathione - metabolism / glutathione peroxidase / glutathione-disulfide reductase / Homeostasis / Humans / Inflammation / Kinases / Medical research / medicine / Medicine, Experimental / Metabolism / Mitochondria / Mitochondria - drug effects / Mitochondria - metabolism / Nebulizers and Vaporizers / Nervous system / Nervous system diseases / neurodegenerative diseases / Neurodegenerative Diseases - drug therapy / Neurons / neuroprotective effect / NF-E2-Related Factor 2 - metabolism / Oxidative stress / Oxidative Stress - drug effects / Peroxidase / Physiology / Proteins / reactive nitrogen species / Reactive oxygen species / Reactive Oxygen Species - metabolism / therapeutics / Thiols / Transcription factors / tripeptides / Xenobiotics