Brain, Learning, and Memory: Role of H2S in Neurodegenerative Diseases

  • B. V. Nagpure
  • Jin-Song BianEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 230)


For more than 300 years, the toxicity of hydrogen sulfide (H2S) has been known to mankind. However, this point of view is changing as an increased interest was observed in H2S biology in the last two decades. The scientific community has succeeded to unravel many important physiological and pathological effects of H2S on mammalian body systems. Thus, H2S is now referred to as a third endogenous gaseous mediator along with nitric oxide and carbon monoxide. Acting as a neuromodulator, H2S facilitates long-term potentiation and regulates intracellular calcium levels, which are important processes in learning and memory. Aberrant endogenous production and metabolism of H2S are implicated in pathogenesis of neurodegenerative diseases including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Various H2S donors have shown beneficial therapeutic effects in neurodegenerative disease models by targeting hallmark pathological events (e.g., amyloid-β production in AD and neuroinflammation in PD). The results obtained from many in vivo studies clearly show that H2S not only prevents neuronal and synaptic deterioration but also improves deficits in memory, cognition, and learning. The anti-inflammatory, antioxidant, and anti-apoptotic effects of H2S underlie its neuroprotective properties. In this chapter, we will overview the current understanding of H2S in context of neurodegenerative diseases, with special emphasis on its corrective effects on impaired learning, memory, and cognition.


Hydrogen sulfide Neurodegeneration Brain Memory Learning Neuroinflammation 



3-Mercaptopyruvate sulfurtransferase



Alzheimer’s disease


Amyloid precursor protein


Cysteine aminotransferase




Central nervous system




Hydrogen sulfide


ATP-sensitive potassium channel


Long-term potentiation


Mitochondrial KATP channel


Sodium hydrogen sulfide


Nuclear factor kappa-light-chain-enhancer of activated B cells


N-methyl-d-aspartic acid


Non-steroidal anti-inflammatory drugs


Parkinson’s disease


Reactive oxygen species



This work was supported by research grants from National University Health System (NUHS B2B research grant-NUHSRO/2011/012/STB/B2B-08) and National Kidney Foundation (NKFRC/2011/01/04).


  1. Abe K, Kimura H (1996) The possible role of hydrogen sulfide as an endogenous neuromodulator. J Neurosci 16(3):1066–1071PubMedGoogle Scholar
  2. Bauer EP, Schafe GE, LeDoux JE (2002) NMDA receptors and L-type voltage-gated calcium channels contribute to long-term potentiation and different components of fear memory formation in the lateral amygdala. J Neurosci 22(12):5239–5249PubMedGoogle Scholar
  3. Berzofsky JA, Peisach J, Blumberg WE (1971) Sulfheme proteins. I. Optical and magnetic properties of sulfmyoglobin and its derivatives. J Biol Chem 246(10):3367–3377PubMedGoogle Scholar
  4. Brown WR, Blair RM, Moody DM, Thore CR, Ahmed S, Robbins ME, Wheeler KT (2007) Capillary loss precedes the cognitive impairment induced by fractionated whole-brain irradiation: a potential rat model of vascular dementia. J Neurol Sci 257(1–2):67–71PubMedGoogle Scholar
  5. Burnett WW, King EG, Grace M, Hall WF (1977) Hydrogen sulfide poisoning: review of 5 years’ experience. Can Med Assoc J 117(11):1277–1280PubMedCentralPubMedGoogle Scholar
  6. Butterfield DA, Castegna A, Lauderback CM, Drake J (2002) Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer’s disease brain contribute to neuronal death. Neurobiol Aging 23(5):655–664PubMedGoogle Scholar
  7. Calvert JW, Jha S, Gundewar S, Elrod JW, Ramachandran A, Pattillo CB, Kevil CG, Lefer DJ (2009) Hydrogen sulfide mediates cardioprotection through Nrf2 signaling. Circ Res 105(4):365–374PubMedCentralPubMedGoogle Scholar
  8. Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59(3):527–605PubMedGoogle Scholar
  9. Chen CC, Shen JW, Chung NC, Min MY, Cheng SJ, Liu IY (2012) Retrieval of context-associated memory is dependent on the Ca(v)3.2 T-type calcium channel. PLoS One 7(1), e29384PubMedCentralPubMedGoogle Scholar
  10. Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM (1998) Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol 55(11):1449–1455PubMedGoogle Scholar
  11. d’Emmanuele di Villa Bianca R, Sorrentino R, Coletta C, Mitidieri E, Rossi A, Vellecco V, Pinto A, Cirino G, Sorrentino R (2011) Hydrogen sulfide-induced dual vascular effect involves arachidonic acid cascade in rat mesenteric arterial bed. J Pharmacol Exp Ther 337(1):59–64PubMedGoogle Scholar
  12. Diwakar L, Ravindranath V (2007) Inhibition of cystathionine-γ-lyase leads to loss of glutathione and aggravation of mitochondrial dysfunction mediated by excitatory amino acid in the CNS. Neurochem Int 50(2):418–426PubMedGoogle Scholar
  13. Dorman DC, Moulin FJ-M, McManus BE, Mahle KC, James RA, Struve MF (2002) Cytochrome oxidase inhibition induced by acute hydrogen sulfide inhalation: correlation with tissue sulfide concentrations in the rat brain, liver, lung, and nasal epithelium. Toxicol Sci 65(1):18–25PubMedGoogle Scholar
  14. Dwyer BE, Raina AK, Perry G, Smith MA (2004) Homocysteine and Alzheimer’s disease: a modifiable risk? Free Radic Biol Med 36(11):1471–1475PubMedGoogle Scholar
  15. Enokido Y, Suzuki E, Iwasawa K, Namekata K, Okazawa H, Kimura H (2005) Cystathionine β-synthase, a key enzyme for homocysteine metabolism, is preferentially expressed in the radial glia/astrocyte lineage of developing mouse CNS. FASEB J 19(13):1854–1856PubMedGoogle Scholar
  16. Eto K, Asada T, Arima K, Makifuchi T, Kimura H (2002) Brain hydrogen sulfide is severely decreased in Alzheimer’s disease. Biochem Biophys Res Commun 293(5):1485–1488PubMedGoogle Scholar
  17. Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M (2005) Global prevalence of dementia: a Delphi consensus study. Lancet 366(9503):2112–2117PubMedCentralPubMedGoogle Scholar
  18. Floyd RA, Carney JM (1992) Free radical damage to protein and DNA: mechanisms involved and relevant observations on brain undergoing oxidative stress. Ann Neurol 32(Suppl):S22–S27PubMedGoogle Scholar
  19. Gangarossa G, Laffray S, Bourinet E, Valjent E (2014) T-type calcium channel Cav3.2 deficient mice show elevated anxiety, impaired memory and reduced sensitivity to psychostimulants. Front Behav Neurosci 8:92PubMedCentralPubMedGoogle Scholar
  20. Garzon J, Rodriguez-Munoz M, Sanchez-Blazquez P (2012) Direct association of Mu-opioid and NMDA glutamate receptors supports their cross-regulation: molecular implications for opioid tolerance. Curr Drug Abuse Rev 5(3):199–226PubMedGoogle Scholar
  21. Giuliani D, Ottani A, Zaffe D, Galantucci M, Strinati F, Lodi R, Guarini S (2013) Hydrogen sulfide slows down progression of experimental Alzheimer’s disease by targeting multiple pathophysiological mechanisms. Neurobiol Learn Mem 104:82–91PubMedGoogle Scholar
  22. Goedert M, Spillantini MG (2006) A century of Alzheimer’s disease. Science 314(5800):777–781PubMedGoogle Scholar
  23. Gong Q-H, Wang Q, Pan L-L, Liu X-H, Huang H, Zhu Y-Z (2010) Hydrogen sulfide attenuates lipopolysaccharide-induced cognitive impairment: a pro-inflammatory pathway in rats. Pharmacol Biochem Behav 96(1):52–58PubMedGoogle Scholar
  24. Gong QH, Wang Q, Pan LL, Liu XH, Xin H, Zhu YZ (2011) S-propargyl-cysteine, a novel hydrogen sulfide-modulated agent, attenuates lipopolysaccharide-induced spatial learning and memory impairment: involvement of TNF signaling and NF-kappaB pathway in rats. Brain Behav Immun 25(1):110–119PubMedGoogle Scholar
  25. Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, Launer LJ, Laurent S, Lopez OL, Nyenhuis D, Petersen RC, Schneider JA, Tzourio C, Arnett DK, Bennett DA, Chui HC, Higashida RT, Lindquist R, Nilsson PM, Roman GC, Sellke FW, Seshadri S (2011) Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association. Stroke 42(9):2672–2713PubMedCentralPubMedGoogle Scholar
  26. Guidotti TL (1996) Hydrogen sulphide. Occup Med (Lond) 46(5):367–371Google Scholar
  27. Guidotti TL (2010) Hydrogen sulfide: advances in understanding human toxicity. Int J Toxicol 29(6):569–581PubMedGoogle Scholar
  28. Guo W, Kan JT, Cheng ZY, Chen JF, Shen YQ, Xu J, Wu D, Zhu YZ (2012) Hydrogen sulfide as an endogenous modulator in mitochondria and mitochondria dysfunction. Oxid Med Cell Longev 2012:878052PubMedCentralPubMedGoogle Scholar
  29. He XL, Yan N, Zhang H, Qi YW, Zhu LJ, Liu MJ, Yan Y (2014) Hydrogen sulfide improves spatial memory impairment and decreases production of Abeta in APP/PS1 transgenic mice. Neurochem Int 67:1–8PubMedGoogle Scholar
  30. Hegde A, Bhatia M (2011) Hydrogen sulfide in inflammation: friend or foe? Inflamm Allergy Drug Targets 10(2):118–122PubMedGoogle Scholar
  31. Hildebrandt TM, Grieshaber MK (2008) Three enzymatic activities catalyze the oxidation of sulfide to thiosulfate in mammalian and invertebrate mitochondria. FEBS J 275(13):3352–3361PubMedGoogle Scholar
  32. Hu LF, Wong PT, Moore PK, Bian JS (2007) Hydrogen sulfide attenuates lipopolysaccharide-induced inflammation by inhibition of p38 mitogen-activated protein kinase in microglia. J Neurochem 100(4):1121–1128PubMedGoogle Scholar
  33. Hu LF, Pan TT, Neo KL, Yong QC, Bian JS (2008) Cyclooxygenase-2 mediates the delayed cardioprotection induced by hydrogen sulfide preconditioning in isolated rat cardiomyocytes. Pflugers Arch 455(6):971–978PubMedGoogle Scholar
  34. Hu LF, Lu M, Wu ZY, Wong PT, Bian JS (2009) Hydrogen sulfide inhibits rotenone-induced apoptosis via preservation of mitochondrial function. Mol Pharmacol 75(1):27–34PubMedGoogle Scholar
  35. Hu LF, Lu M, Tiong CX, Dawe GS, Hu G, Bian JS (2010) Neuroprotective effects of hydrogen sulfide on Parkinson’s disease rat models. Aging Cell 9(2):135–146PubMedGoogle Scholar
  36. Hu LF, Lu M, Hon Wong PT, Bian JS (2011) Hydrogen sulfide: neurophysiology and neuropathology. Antioxid Redox Signal 15(2):405–419PubMedGoogle Scholar
  37. Iadecola C (2013) The pathobiology of vascular dementia. Neuron 80(4):844–866PubMedGoogle Scholar
  38. Ishigami M, Hiraki K, Umemura K, Ogasawara Y, Ishii K, Kimura H (2009) A source of hydrogen sulfide and a mechanism of its release in the brain. Antioxid Redox Signal 11(2):205–214PubMedGoogle Scholar
  39. Jiang LH, Wang J, Wei XL, Liang QY, Cheng TT (2012) Exogenous sodium hydrosulfide can attenuate naloxone-precipitated withdrawal syndromes and affect cAMP signaling pathway in heroin-dependent rat’s nucleus accumbens. Eur Rev Med Pharmacol Sci 16(14):1974–1982PubMedGoogle Scholar
  40. Kabil O, Banerjee R (2010) Redox biochemistry of hydrogen sulfide. J Biol Chem 285(29):21903–21907PubMedCentralPubMedGoogle Scholar
  41. Kabil O, Banerjee R (2014) Enzymology of H2S biogenesis, decay and signaling. Antioxid Redox Signal 20(5):770–782PubMedCentralPubMedGoogle Scholar
  42. Kandel ER (2001) The molecular biology of memory storage: a dialogue between genes and synapses. Science 294(5544):1030–1038PubMedGoogle Scholar
  43. Kida K, Yamada M, Tokuda K, Marutani E, Kakinohana M, Kaneki M, Ichinose F (2011) Inhaled hydrogen sulfide prevents neurodegeneration and movement disorder in a mouse model of Parkinson’s disease. Antioxid Redox Signal 15(2):343–352PubMedCentralPubMedGoogle Scholar
  44. Kimura H (2011) Hydrogen sulfide: its production, release and functions. Amino Acids 41(1):113–121PubMedGoogle Scholar
  45. Kimura H (2014) Production and physiological effects of hydrogen sulfide. Antioxid Redox Signal 20(5):783–793PubMedCentralPubMedGoogle Scholar
  46. Kimura Y, Kimura H (2004) Hydrogen sulfide protects neurons from oxidative stress. FASEB J 18(10):1165–1167PubMedGoogle Scholar
  47. Kimura Y, Dargusch R, Schubert D, Kimura H (2006) Hydrogen sulfide protects HT22 neuronal cells from oxidative stress. Antioxid Redox Signal 8(3-4):661–670PubMedGoogle Scholar
  48. Kimura Y, Goto Y, Kimura H (2010) Hydrogen sulfide increases glutathione production and suppresses oxidative stress in mitochondria. Antioxid Redox Signal 12(1):1–13PubMedGoogle Scholar
  49. Kohn C, Dubrovska G, Huang Y, Gollasch M (2012) Hydrogen sulfide: potent regulator of vascular tone and stimulator of angiogenesis. Int J Biomed Sci 8(2):81–86PubMedCentralPubMedGoogle Scholar
  50. Lambert TW, Goodwin VM, Stefani D, Strosher L (2006) Hydrogen sulfide (H2S) and sour gas effects on the eye. A historical perspective. Sci Total Environ 367(1):1–22PubMedGoogle Scholar
  51. Lee SW, Hu YS, Hu LF, Lu Q, Dawe GS, Moore PK, Wong PT, Bian JS (2006) Hydrogen sulphide regulates calcium homeostasis in microglial cells. Glia 54(2):116–124PubMedGoogle Scholar
  52. Lee SW, Cheng Y, Moore PK, Bian J-S (2007) Hydrogen sulphide regulates intracellular pH in vascular smooth muscle cells. Biochem Biophys Res Commun 358(4):1142–1147PubMedGoogle Scholar
  53. Lee M, Schwab C, Yu S, McGeer E, McGeer PL (2009) Astrocytes produce the antiinflammatory and neuroprotective agent hydrogen sulfide. Neurobiol Aging 30(10):1523–1534PubMedGoogle Scholar
  54. Lee M, Tazzari V, Giustarini D, Rossi R, Sparatore A, Del Soldato P, McGeer E, McGeer PL (2010) Effects of hydrogen sulfide-releasing L-DOPA derivatives on glial activation: potential for treating Parkinson disease. J Biol Chem 285(23):17318–17328PubMedCentralPubMedGoogle Scholar
  55. Lim JJ, Liu YH, Khin ES, Bian JS (2008) Vasoconstrictive effect of hydrogen sulfide involves downregulation of cAMP in vascular smooth muscle cells. Am J Physiol Cell Physiol 295(5):C1261–C1270PubMedGoogle Scholar
  56. Liu C, Wu J, Gu J, Xiong Z, Wang F, Wang J, Wang W, Chen J (2007) Baicalein improves cognitive deficits induced by chronic cerebral hypoperfusion in rats. Pharmacol Biochem Behav 86(3):423–430PubMedGoogle Scholar
  57. Liu XQ, Liu XQ, Jiang P, Huang H, Yan Y (2008) 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 88(32):2246–2249PubMedGoogle Scholar
  58. Liu YH, Lu M, Hu LF, Wong PT, Webb GD, Bian JS (2012) Hydrogen sulfide in the mammalian cardiovascular system. Antioxid Redox Signal 17(1):141–185PubMedGoogle Scholar
  59. Lu M, Hu LF, Hu G, Bian JS (2008) Hydrogen sulfide protects astrocytes against H(2)O(2)-induced neural injury via enhancing glutamate uptake. Free Radic Biol Med 45(12):1705–1713PubMedGoogle Scholar
  60. Malaguarnera L, Motta M, Di Rosa M, Anzaldi M, Malaguarnera M (2006) Interleukin-18 and transforming growth factor-beta 1 plasma levels in Alzheimer’s disease and vascular dementia. Neuropathology 26(4):307–312PubMedGoogle Scholar
  61. Mallmann RT, Elgueta C, Sleman F, Castonguay J, Wilmes T, van den Maagdenberg A, Klugbauer N (2013) Ablation of Ca(V)2.1 voltage-gated Ca(2)(+) channels in mouse forebrain generates multiple cognitive impairments. PLoS One 8(10), e78598PubMedCentralPubMedGoogle Scholar
  62. Mark G, Naumov S, von Sonntag C (2011) The reaction of ozone with bisulfide (HS−) in aqueous solution – mechanistic aspects. Ozone Sci Eng 33(1):37–41Google Scholar
  63. Mikami Y, Shibuya N, Kimura Y, Nagahara N, Yamada M, Kimura H (2011) Hydrogen sulfide protects the retina from light-induced degeneration by the modulation of Ca2+ influx. J Biol Chem 286(45):39379–39386PubMedCentralPubMedGoogle Scholar
  64. Milby TH, Baselt RC (1999) Hydrogen sulfide poisoning: clarification of some controversial issues. Am J Ind Med 35(2):192–195PubMedGoogle Scholar
  65. Milner B, Squire LR, Kandel ER (1998) Cognitive neuroscience and the study of memory. Neuron 20(3):445–468PubMedGoogle Scholar
  66. Morrison LD, Smith DD, Kish SJ (1996) Brain S-adenosylmethionine levels are severely decreased in Alzheimer’s disease. J Neurochem 67(3):1328–1331PubMedGoogle Scholar
  67. Nagai Y, Tsugane M, Oka J, Kimura H (2004) Hydrogen sulfide induces calcium waves in astrocytes. FASEB J 18(3):557–559PubMedGoogle Scholar
  68. Nagpure BV, Bian JS (2014) Hydrogen sulfide inhibits A2A adenosine receptor agonist induced beta-amyloid production in SH-SY5Y neuroblastoma cells via a cAMP dependent pathway. PLoS One 9(2), e88508PubMedCentralPubMedGoogle Scholar
  69. Nimmrich V, Ebert U (2009) Is Alzheimer’s disease a result of presynaptic failure? Synaptic dysfunctions induced by oligomeric beta-amyloid. Rev Neurosci 20(1):1–12PubMedGoogle Scholar
  70. Nimmrich V, Grimm C, Draguhn A, Barghorn S, Lehmann A, Schoemaker H, Hillen H, Gross G, Ebert U, Bruehl C (2008) Amyloid beta oligomers (A beta(1-42) globulomer) suppress spontaneous synaptic activity by inhibition of P/Q-type calcium currents. J Neurosci 28(4):788–797PubMedGoogle Scholar
  71. O’Suilleabhain PE, Sung V, Hernandez C, Lacritz L, Dewey RB Jr, Bottiglieri T, Diaz-Arrastia R (2004) Elevated plasma homocysteine level in patients with Parkinson disease: motor, affective, and cognitive associations. Arch Neurol 61(6):865–868PubMedGoogle Scholar
  72. Pan TT, Feng ZN, Lee SW, Moore PK, Bian JS (2006) Endogenous hydrogen sulfide contributes to the cardioprotection by metabolic inhibition preconditioning in the rat ventricular myocytes. J Mol Cell Cardiol 40(1):119–130PubMedGoogle Scholar
  73. Polhemus DJ, Calvert JW, Butler J, Lefer DJ (2014) The cardioprotective actions of hydrogen sulfide in acute myocardial infarction and heart failure. Scientifica (Cairo) 2014:768607Google Scholar
  74. Prior MG, Sharma AK, Yong S, Lopez A (1988) Concentration-time interactions in hydrogen sulphide toxicity in rats. Can J Vet Res 52(3):375PubMedCentralPubMedGoogle Scholar
  75. Reitz C, Brayne C, Mayeux R (2011) Epidemiology of Alzheimer disease. Nat Rev Neurol 7(3):137–152PubMedCentralPubMedGoogle Scholar
  76. Robert K, Vialard F, Thiery E, Toyama K, Sinet PM, Janel N, London J (2003) Expression of the cystathionine beta synthase (CBS) gene during mouse development and immunolocalization in adult brain. J Histochem Cytochem 51(3):363–371PubMedGoogle Scholar
  77. Ronk R, White MK (1985) Hydrogen sulfide and the probabilities of ‘inhalation’ through a tympanic membrane defect. J Occup Environ Med 27(5):337–340Google Scholar
  78. Sastre C, Baillif-Couniou V, Kintz P, Cirimele V, Bartoli C, Christia-Lotter M-A, Piercecchi-Marti M-D, Leonetti G, Pelissier-Alicot A-L (2013) Fatal accidental hydrogen sulfide poisoning: a domestic case. J Forensic Sci 58:S280–S284PubMedGoogle Scholar
  79. Sekiguchi F, Miyamoto Y, Kanaoka D, Ide H, Yoshida S, Ohkubo T, Kawabata A (2014) Endogenous and exogenous hydrogen sulfide facilitates T-type calcium channel currents in Cav3.2-expressing HEK293 cells. Biochem Biophys Res Commun 445(1):225–229PubMedGoogle Scholar
  80. Seoane A, Massey PV, Keen H, Bashir ZI, Brown MW (2009) L-type voltage-dependent calcium channel antagonists impair perirhinal long-term recognition memory and plasticity processes. J Neurosci 29(30):9534–9544PubMedGoogle Scholar
  81. Shibuya N, Kimura H (2013) Production of hydrogen sulfide from d-cysteine and its therapeutic potential. Front Endocrinol (Lausanne) 4:87Google Scholar
  82. Shibuya N, Tanaka M, Yoshida M, Ogasawara Y, Togawa T, Ishii K, Kimura H (2009) 3-Mercaptopyruvate sulfurtransferase produces hydrogen sulfide and bound sulfane sulfur in the brain. Antioxid Redox Signal 11(4):703–714PubMedGoogle Scholar
  83. Singh S, Padovani D, Leslie RA, Chiku T, Banerjee R (2009) Relative contributions of cystathionine beta-synthase and gamma-cystathionase to H2S biogenesis via alternative trans-sulfuration reactions. J Biol Chem 284(33):22457–22466PubMedCentralPubMedGoogle Scholar
  84. Sparatore A, Santus G, Giustarini D, Rossi R, Del Soldato P (2011) Therapeutic potential of new hydrogen sulfide-releasing hybrids. Expert Rev Clin Pharmacol 4(1):109–121PubMedGoogle Scholar
  85. Stein A, Bailey SM (2013) Redox biology of hydrogen sulfide: implications for physiology, pathophysiology, and pharmacology. Redox Biol 1(1):32–39PubMedCentralPubMedGoogle Scholar
  86. Stephan BC, Brayne C (2008) Vascular factors and prevention of dementia. Int Rev Psychiatry 20(4):344–356PubMedGoogle Scholar
  87. Tang XQ, Yang CT, Chen J, Yin WL, Tian SW, Hu B, Feng JQ, Li YJ (2008) Effect of hydrogen sulphide on beta-amyloid-induced damage in PC12 cells. Clin Exp Pharmacol Physiol 35(2):180–186PubMedGoogle Scholar
  88. Tang XQ, Shen XT, Huang YE, Chen RQ, Ren YK, Fang HR, Zhuang YY, Wang CY (2011) Inhibition of endogenous hydrogen sulfide generation is associated with homocysteine-induced neurotoxicity: role of ERK1/2 activation. J Mol Neurosci 45(1):60–67PubMedGoogle Scholar
  89. Tang X-Q, Zhuang Y-Y, Zhang P, Fang H-R, Zhou C-F, Gu H-F, Zhang H, Wang C-Y (2013) Formaldehyde impairs learning and memory involving the disturbance of hydrogen sulfide generation in the hippocampus of rats. J Mol Neurosci 49(1):140–149PubMedGoogle Scholar
  90. Tansy MF, Kendall FM, Fantasia J, Landin WE, Oberly R, Sherman W (1981) Acute and subchronic toxicity studies of rats exposed to vapors of methyl mercaptan and other reduced‐sulfur compounds. J Toxicol Environ Health 8(1-2):71–88PubMedGoogle Scholar
  91. Thompson AD, Scaglione KM, Prensner J, Gillies AT, Chinnaiyan A, Paulson HL, Jinwal UK, Dickey CA, Gestwicki JE (2012) Analysis of the tau-associated proteome reveals that exchange of Hsp70 for Hsp90 is involved in tau degradation. ACS Chem Biol 7(10):1677–1686PubMedCentralPubMedGoogle Scholar
  92. Tiong CX, Lu M, Bian JS (2010) Protective effect of hydrogen sulphide against 6-OHDA-induced cell injury in SH-SY5Y cells involves PKC/PI3K/Akt pathway. Br J Pharmacol 161(2):467–480PubMedCentralPubMedGoogle Scholar
  93. Truong DH, Eghbal MA, Hindmarsh W, Roth SH, O’Brien PJ (2006) Molecular mechanisms of hydrogen sulfide toxicity. Drug Metab Rev 38(4):733–744PubMedGoogle Scholar
  94. Turner RM, Fairhurst S, Britain G (1990) Toxicology of substances in relation to major hazards: hydrogen sulphide. HM Stationery Office, LondonGoogle Scholar
  95. Uttara B, Singh AV, Zamboni P, Mahajan RT (2009) Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol 7(1):65–74PubMedCentralPubMedGoogle Scholar
  96. van Kampen EJ, Zijlstra WG (1983) Spectrophotometry of hemoglobin and hemoglobin derivatives. Adv Clin Chem 23:199–257PubMedGoogle Scholar
  97. Vorobets VS, Kovach SK, Kolbasov GY (2002) Distribution of Ion species and formation of ion pairs in concentrated polysulfide solutions in photoelectrochemical transducers. Rus J Appl Chem 75(2):229–234Google Scholar
  98. Voss K, Combs B, Patterson KR, Binder LI, Gamblin TC (2012) Hsp70 alters tau function and aggregation in an isoform specific manner. Biochemistry 51(4):888–898PubMedCentralPubMedGoogle Scholar
  99. Wang D (1989) A review of 152 cases of acute poisoning of hydrogen sulfide. Zhonghua Yi Xue Za Zhi 23(6):330–332Google Scholar
  100. Warenycia MW, Steele JA, Karpinski E, Reiffenstein RJ (1989) Hydrogen sulfide in combination with taurine or cysteic acid reversibly abolishes sodium currents in neuroblastoma cells. Neurotoxicology 10(2):191–199PubMedGoogle Scholar
  101. Whiteman M, Winyard PG (2011) Hydrogen sulfide and inflammation: the good, the bad, the ugly and the promising. Expert Rev Clin Pharmacol 4(1):13–32PubMedGoogle Scholar
  102. Whiteman M, Armstrong JS, Chu SH, Jia-Ling S, Wong BS, Cheung NS, Halliwell B, Moore PK (2004) The novel neuromodulator hydrogen sulfide: an endogenous peroxynitrite ‘scavenger’? J Neurochem 90(3):765–768PubMedGoogle Scholar
  103. Xie L, Tiong CX, Bian J-S (2012) Hydrogen sulfide protects SH-SY5Y cells against 6-hydroxydopamine-induced endoplasmic reticulum stress. Am J Physiol Cell Physiol 303(1):C81–C91PubMedGoogle Scholar
  104. Xie L, Hu LF, Teo XQ, Tiong CX, Tazzari V, Sparatore A, Del Soldato P, Dawe GS, Bian JS (2013) Therapeutic effect of hydrogen sulfide-releasing L-Dopa derivative ACS84 on 6-OHDA-induced Parkinson’s disease rat model. PLoS One 8(4), e60200PubMedCentralPubMedGoogle Scholar
  105. Xuan A, Long D, Li J, Ji W, Zhang M, Hong L, Liu J (2012) Hydrogen sulfide attenuates spatial memory impairment and hippocampal neuroinflammation in beta-amyloid rat model of Alzheimer’s disease. J Neuroinflammation 9:202PubMedCentralPubMedGoogle Scholar
  106. Yamanishi T, Tuboi S (1981) The mechanism of the L-cystine cleavage reaction catalyzed by rat liver gamma-cystathionase. J Biochem 89(6):1913–1921PubMedGoogle Scholar
  107. Yang G, Wu L, Jiang B, Yang W, Qi J, Cao K, Meng Q, Mustafa AK, Mu W, Zhang S, Snyder SH, Wang R (2008) H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase. Science 322(5901):587–590PubMedCentralPubMedGoogle Scholar
  108. Yang HY, Wu ZY, Wood M, Whiteman M, Bian JS (2013) Hydrogen sulfide attenuates opioid dependence by suppression of adenylate cyclase/cAMP pathway. Antioxid Redox Signal 20(1):31–41PubMedGoogle Scholar
  109. Yin WL, He JQ, Hu B, Jiang ZS, Tang XQ (2009) Hydrogen sulfide inhibits MPP(+)-induced apoptosis in PC12 cells. Life Sci 85(7-8):269–275PubMedGoogle Scholar
  110. Yong QC, Choo CH, Tan BH, Low CM, Bian JS (2010) Effect of hydrogen sulfide on intracellular calcium homeostasis in neuronal cells. Neurochem Int 56(3):508–515PubMedGoogle Scholar
  111. Zhang LM, Jiang CX, Liu DW (2009) Hydrogen sulfide attenuates neuronal injury induced by vascular dementia via inhibiting apoptosis in rats. Neurochem Res 34(11):1984–1992PubMedGoogle Scholar
  112. Zhang H, Gao Y, Zhao F, Dai Z, Meng T, Tu S, Yan Y (2011) Hydrogen sulfide reduces mRNA and protein levels of beta-site amyloid precursor protein cleaving enzyme 1 in PC12 cells. Neurochem Int 58(2):169–175PubMedGoogle Scholar
  113. Zhao Y, Biggs TD, Xian M (2014) Hydrogen sulfide (HS) releasing agents: chemistry and biological applications. Chem Commun (Camb)Google Scholar
  114. Zhou X, Cao Y, Ao G, Hu L, Liu H, Wu J, Wang X, Jin M, Zheng S, Zhen X, Alkayed NJ, Jia J, Cheng J (2014) CaMKKbeta-dependent activation of AMP-activated protein kinase is critical to suppressive effects of hydrogen sulfide on neuroinflammation. Antioxid Redox Signal 21(12):1741–1758PubMedGoogle Scholar
  115. Zhu L, Chen X, He X, Qi Y, Yan Y (2014) Effect of exogenous hydrogen sulfide on BACE-1 enzyme expression and beta-amyloid peptide metabolism in high-glucose primary neuronal culture. Nan Fang Yi Ke Da Xue Xue Bao 34(4):504–506, 510PubMedGoogle Scholar
  116. Zoccolella S, dell’Aquila C, Specchio LM, Logroscino G, Lamberti P (2010) Elevated homocysteine levels in Parkinson’s disease: is there anything besides L-dopa treatment? Curr Med Chem 17(3):213–221PubMedGoogle Scholar

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© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of PharmacologyYong Loo Lin School of Medicine, National University of SingaporeSingaporeSingapore

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