Cystathionine γ-lyase is a major regulator of cognitive function through neurotrophin signaling and neurogenesis
Abstract
Cystathionine γ-lyase (CSE), the enzyme responsible for neuronal cysteine and hydrogen sulfide production, is dysregulated in aging and neurodegenerative diseases including Alzheimer’s disease and Huntington’s disease, both marked by cognitive decline in addition to motor deficits. To determine whether CSE loss directly causes cognitive decline, we genetically ablated CSE in mice. This loss was sufficient to induce oxidative damage, compromise blood–brain barrier integrity, impair neurogenesis and neurotrophin signaling, and elicit cognitive deficits. Global proteomic analysis further revealed molecular alterations that contribute to impaired neurogenesis. Our findings establish CSE as an essential guardian of homeostatic brain health and identify it as a potential therapeutic target for neurodegenerative disorders.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (17)
Suwarna Chakraborty
Department of Physiology, Pharmacology, & Therapeutics, Johns Hopkins University School of Medicine
Sunil Jamuna Tripathi
Department of Physiology, Pharmacology, & Therapeutics, Johns Hopkins University School of Medicine
Edwin Vázquez-Rosa
Department of Psychiatry, Case Western Reserve University
Kalyani Chaubey
Department of Psychiatry, Case Western Reserve University
Hisashi Fujioka
Cryo-Electron Microscopy Core Facility, Case Western Reserve University School of Medicine
Emiko Miller
Department of Psychiatry, Case Western Reserve University
Richa Tyagi
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine
Thibaut Vignane
Leibniz Institute for Analytical Sciences
Sudarshana M. Sharma
Department of Biochemistry and Molecular Biology and Hollings Cancer Center, Medical University of South Carolina
Bobby Thomas
Darby Children’s Research Institute, Medical University of South Carolina
Zachary M. Weil
Department of Neuroscience, Rockefeller Neuroscience Institute, West Virginia University School of Medicine
Randy J. Nelson
Department of Neuroscience, Rockefeller Neuroscience Institute, West Virginia University School of Medicine
Milos R. Filipovic
Leibniz Institute for Analytical Sciences
Benjamin C. Orsburn
Department of Physiology, Pharmacology, & Therapeutics, Johns Hopkins University School of Medicine
Solomon H. Snyder
Department of Physiology, Pharmacology, & Therapeutics, Johns Hopkins University School of Medicine
Andrew A. Pieper
Department of Psychiatry, Case Western Reserve University
Bindu D. Paul
Department of Physiology, Pharmacology, & Therapeutics, Johns Hopkins University School of Medicine