Priyanka Soni, Shravan Paswan, Bindu D Paul, Bobby Thomas
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引用次数: 0
Abstract
Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), represent a significant global health burden due to their progressive and debilitating nature. While the etiology of these disorders is multifaceted, oxidative stress, resulting from an imbalance between the generation of reactive oxygen species (ROS) and neuronal antioxidant stress responses, has emerged as a pivotal factor in their pathogenesis. Amongst the cellular defense mechanisms counteracting oxidative stress, signaling cascades regulated by the nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) signaling axis, play a crucial role. Nrf2 signaling is modulated at multiple levels and regulates redox homeostasis and other cellular processes such as expression of neuroprotective genes, resolution of neuroinflammation, stimulating mitochondrial bioenergetics, facilitating cellular repair, and proteostasis. In recent years, the gaseous molecule or gasotransmitter, hydrogen sulfide (H2S), was shown to modulate Nrf2-mediated signaling through processes that include disruption of Keap1-Nrf2 interaction, leading to enhanced Nrf2 activation. This review explores the intricate relationship between hydrogen sulfide and Nrf2-Keap1 signaling, highlighting their potential to counteract neurodegenerative processes. The interplay between H2S and Nrf2 signaling underscores their potential as endogenous regulators of cellular resilience against neurodegeneration. Understanding how gasotransmitters fine-tune the Nrf2-Keap1 pathway opens up new avenues for therapeutic interventions in these neurodegenerative disorders. By elucidating how gasotransmitters influence Nrf2-mediated responses, we aim to underscore promising therapeutic strategies that target oxidative damage, modulate neuroinflammation, and enhance neuronal survival pathways in neurodegenerative diseases.
期刊介绍：
Neurotherapeutics® is the journal of the American Society for Experimental Neurotherapeutics (ASENT). Each issue provides critical reviews of an important topic relating to the treatment of neurological disorders written by international authorities.
The Journal also publishes original research articles in translational neuroscience including descriptions of cutting edge therapies that cross disciplinary lines and represent important contributions to neurotherapeutics for medical practitioners and other researchers in the field.
Neurotherapeutics ® delivers a multidisciplinary perspective on the frontiers of translational neuroscience, provides perspectives on current research and practice, and covers social and ethical as well as scientific issues.
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