Redox Molecules in Aging and Neurodegenerative Disorders.
Redox Molecules in Aging and Neurodegenerative Disorders.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Memphis, US · Author affiliation
Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.Location evidence
Voronezh, RU · Author affiliation
Department of Medical Biochemistry, Molecular and Cell Biology, Voronezh State University, Universitetskaya Sq. 1, Voronezh 394018, Russia.Location evidence
Moscow, RU · Author affiliation
Department of Medical Biochemistry, Faculty of Biomedicine, Pirogov Russian National Research Medical University, Ostrovitianov St. 1, Moscow 117997, Russia.Location evidence
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Original abstract
Oxidative stress is a key player in the pathogenesis of aging and various neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and multiple sclerosis (MS), among others. Coupled molecules involved in chemical reduction-oxidation (redox) reactions regulate central signaling pathways and ensure the activation of cytoprotective mechanisms as needed. Such redox couples include oxidized and reduced forms of nicotinamide adenine dinucleotide (NAD+/NADH), nicotinamide adenine dinucleotide phosphate (NADP+/NADPH), and glutathione (GSSG/GSH), respectively. Under pathological conditions, concentrations of NAD+, NADPH, and GSH decrease, and an imbalance between the oxidized and reduced forms of these molecules develops. The current review focuses on the mechanisms that underlie these changes and their potential consequences for neurodegenerative processes and aging. The review also evaluates experimental studies on metabolic and genetic abnormalities associated with alterations in NAD+, NADPH, and GSH concentrations and highlights current research on strategies to regulate these compounds for neuroprotective purposes. Special attention is paid to understanding the interconnection between disturbed redox homeostasis and mitochondrial dysfunction, as this crosstalk is increasingly recognized as a crucial step in neurodegeneration. Integration of biochemical, genetic, and therapeutic perspectives provides a comprehensive understanding of redox imbalance in the pathogenesis of aging and neurodegenerative disorders. Therefore, these insights may contribute to the development of innovative interventions that target redox homeostasis, with the potential of increasing the human lifespan.