Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Lieber Institute for Brain Development, Baltimore, MD, USA.
Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA; Department of Neurosciences, Case Western Reserve University, School of Medicine, Cleveland, OH, USA; Department of Pathology, Case Western Reserve University, School of Medicine, Cleveland, OH, USA; Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; Brain Health Medicines Center, Harrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Geriatric Psychiatry, GRECC, Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA.
Curr Opin Chem Biol. 2024 Oct;82:102511. doi: 10.1016/j.cbpa.2024.102511. Epub 2024 Aug 13.
The ancient messenger molecule hydrogen sulfide (HS) modulates myriad signaling cascades and has been conserved across evolutionary boundaries. Although traditionally known as an environmental toxin, HS is also synthesized endogenously to exert modulatory and homeostatic effects in a broad array of physiologic functions. Notably, HS levels are tightly physiologically regulated, as both its excess and paucity can be toxic. Accumulating evidence has revealed pivotal roles for HS in neuroprotection and normal cognitive function, and HS homeostasis is dysregulated in neurodegenerative conditions. Here, we review the normal neuroprotective roles of HS that go awry in Alzheimer's disease, the most common form of neurodegenerative disease.
古老的信使分子硫化氢(HS)调节着无数的信号级联反应,并且在进化过程中得到了保守。虽然传统上被认为是一种环境毒素,但 HS 也在内源性合成,以在广泛的生理功能中发挥调节和内稳态作用。值得注意的是,HS 水平受到严格的生理调节,因为其过多和缺乏都会产生毒性。越来越多的证据表明 HS 在神经保护和正常认知功能中起着关键作用,而 HS 内稳态在神经退行性疾病中失调。在这里,我们回顾了 HS 在阿尔茨海默病(最常见的神经退行性疾病)中正常的神经保护作用,这些作用在这种疾病中出现了异常。