Neuroprotective Signaling by Hydrogen Sulfide and Its Dysregulation in Alzheimer's Disease

Overview

Journal Curr Opin Chem Biol

Publisher Elsevier

Specialty Biochemistry

Date 2024 Aug 14

PMID 39142018

Authors

Bindu D Paul

Andrew A Pieper

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

An Imidazo-Pyridin-Derived Fluorescent Probe for Monitoring Hydrogen Sulfide in Chinese Medicinal Materials.

Mao L, Han X, Wu H, Xu L, Zheng H, Wang F J Fluoresc. 2025; .

PMID: 39903389 DOI: 10.1007/s10895-024-04083-z.

References

Amagase H . Clarifying the real bioactive constituents of garlic. J Nutr. 2006; 136(3 Suppl):716S-725S. DOI: 10.1093/jn/136.3.716S. View

Braak H, Braak E . Staging of Alzheimer's disease-related neurofibrillary changes. Neurobiol Aging. 1995; 16(3):271-8; discussion 278-84. DOI: 10.1016/0197-4580(95)00021-6. View

Macleod G, McKeown C, Hall A, Russell M . Hydrothermal and oceanic pH conditions of possible relevance to the origin of life. Orig Life Evol Biosph. 1994; 24(1):19-41. DOI: 10.1007/BF01582037. View

Paul B . Neuroprotective Roles of the Reverse Transsulfuration Pathway in Alzheimer's Disease. Front Aging Neurosci. 2021; 13:659402. PMC: 8007787. DOI: 10.3389/fnagi.2021.659402. View

Goldford J, Hartman H, Marsland 3rd R, Segre D . Environmental boundary conditions for the origin of life converge to an organo-sulfur metabolism. Nat Ecol Evol. 2019; 3(12):1715-1724. PMC: 6881557. DOI: 10.1038/s41559-019-1018-8. View

Seshadri S, Beiser A, Selhub J, Jacques P, Rosenberg I, DAgostino R . Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med. 2002; 346(7):476-83. DOI: 10.1056/NEJMoa011613. View

Paul B . Cysteine metabolism and hydrogen sulfide signaling in Huntington's disease. Free Radic Biol Med. 2022; 186:93-98. PMC: 10066926. DOI: 10.1016/j.freeradbiomed.2022.05.005. View

Yang G, Wu L, Jiang B, Yang W, Qi J, Cao K . H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase. Science. 2008; 322(5901):587-90. PMC: 2749494. DOI: 10.1126/science.1162667. View

Liu X, Liu X, Jiang P, Huang H, Yan Y . [Plasma levels of endogenous hydrogen sulfide and homocysteine in patients with Alzheimer's disease and vascular dementia and the significance thereof]. Zhonghua Yi Xue Za Zhi. 2008; 88(32):2246-9. View

10.

Kashfi K, Olson K . Biology and therapeutic potential of hydrogen sulfide and hydrogen sulfide-releasing chimeras. Biochem Pharmacol. 2012; 85(5):689-703. PMC: 3566320. DOI: 10.1016/j.bcp.2012.10.019. View

11.

Sen N, Paul B, Gadalla M, Mustafa A, Sen T, Xu R . Hydrogen sulfide-linked sulfhydration of NF-κB mediates its antiapoptotic actions. Mol Cell. 2012; 45(1):13-24. PMC: 3261430. DOI: 10.1016/j.molcel.2011.10.021. View

12.

Barker S, Paul B, Pieper A . Increased Risk of Aging-Related Neurodegenerative Disease after Traumatic Brain Injury. Biomedicines. 2023; 11(4). PMC: 10135798. DOI: 10.3390/biomedicines11041154. View

13.

Furuie H, Kimura Y, Akaishi T, Yamada M, Miyasaka Y, Saitoh A . Hydrogen sulfide and polysulfides induce GABA/glutamate/D-serine release, facilitate hippocampal LTP, and regulate behavioral hyperactivity. Sci Rep. 2023; 13(1):17663. PMC: 10618189. DOI: 10.1038/s41598-023-44877-y. View

14.

Stamler J, Simon D, Osborne J, Mullins M, Jaraki O, Michel T . S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds. Proc Natl Acad Sci U S A. 1992; 89(1):444-8. PMC: 48254. DOI: 10.1073/pnas.89.1.444. View

15.

Shen X, Carlstrom M, Borniquel S, Jadert C, Kevil C, Lundberg J . Microbial regulation of host hydrogen sulfide bioavailability and metabolism. Free Radic Biol Med. 2013; 60:195-200. PMC: 4077044. DOI: 10.1016/j.freeradbiomed.2013.02.024. View

16.

Lindwall G, Cole R . Phosphorylation affects the ability of tau protein to promote microtubule assembly. J Biol Chem. 1984; 259(8):5301-5. View

17.

Selkoe D, Wolfe M . Presenilin: running with scissors in the membrane. Cell. 2007; 131(2):215-21. DOI: 10.1016/j.cell.2007.10.012. View

18.

Warenycia M, Goodwin L, Benishin C, Reiffenstein R, Francom D, Taylor J . Acute hydrogen sulfide poisoning. Demonstration of selective uptake of sulfide by the brainstem by measurement of brain sulfide levels. Biochem Pharmacol. 1989; 38(6):973-81. DOI: 10.1016/0006-2952(89)90288-8. View

19.

Gomez-Isla T, HOLLISTER R, West H, Mui S, Growdon J, Petersen R . Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease. Ann Neurol. 1997; 41(1):17-24. DOI: 10.1002/ana.410410106. View

20.

Zhao H, Chan S, Ng Y, Wong P . Brain 3-Mercaptopyruvate Sulfurtransferase (3MST): Cellular Localization and Downregulation after Acute Stroke. PLoS One. 2013; 8(6):e67322. PMC: 3689812. DOI: 10.1371/journal.pone.0067322. View