Skip to main content
SpringerLink
Log in

GAPDH: β-Amyloid Mediated Iron Accumulation in Alzheimer’s Disease: A New Paradigm for Oxidative Stress Induction in Neurodegenerative Disorders

  • Chapter
  • First Online:
Studies on Alzheimer's Disease

Abstract

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder characterized clinically by dementia, loss of memory, and cognitive dysfunction. Although a number of molecular, biochemical, and cellular defects have been identified, the exact molecular mechanism(s) which underlie this disease are unknown. Of particular interest may be aberrant protein–protein interactions, especially with the amyloid protein which may lead not only to plaque development but also to alterations in cell function due to protein depletion. In that regard, recent evidence suggests a specific interaction of the β-amyloid precursor protein (β-APP) and the β-amyloid protein (β-AP) with glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The latter was thought to be a classical glycolytic protein of seemingly little interest. However, recent studies suggest that it is a multifunctional protein with diverse activities independent of its role in energy production. Further, it exhibits a diverse subcellular localization in the nucleus, membrane, and cytosol which may be not only directly related to its functional diversity but also may represent an intracellular equilibrium in the regulation of GAPDH expression. Accordingly, we shall consider the hypothesis that the formation of β-APP or β-AP–GAPDH protein–protein complexes alters both GAPDH function and its subcellular distribution. In particular, as recent studies indicate a fundamental role for membrane GAPDH in cellular iron uptake, transport, and metabolism, the formation of either β-APP–GAPDH or β-AP–GAPDH complexes may facilitate iron accumulation (a known characteristic of Alzheimer’s disease), thereby increasing oxidative stress as a consequence of an intracellular Fenton reaction. This pleiotropic effect of GAPDH binding could serve as a unifying hypothesis providing an initiating event in AD.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Sirover MA. New insight into an old protein: the functional diversity of mammalian glyceraldehyde-3-phosphate dehydrogenase. Biochim Biophys Acta. 1999;1432:159–84.

    Article  PubMed  CAS  Google Scholar 

  2. Sirover MA. New nuclear functions of the glycolytic protein glyceraldehyde-3-phosphate dehydrogenase. J Cell Biochem. 2005;95:45–52.

    Article  PubMed  CAS  Google Scholar 

  3. Sirover MA. On the functional diversity of glyceraldehyde-3-phosphate dehydrogenase: Biochemical mechanisms and regulatory control. Biochim Biophys Acta. 2011;1810:741–51.

    Article  PubMed  CAS  Google Scholar 

  4. Sirover MA. Subcellular dynamics of multifunctional protein regulation: mechanisms of GAPDH intracellular translocation. J Cell Biochem. 2012;113:2193–200.

    Article  PubMed  CAS  Google Scholar 

  5. Tristan C, Shahani N, Sedlak TW, Sawa A. The diverse functions of GAPDH: views from different subcellular compartments. Cell Signal. 2011;23:317–23.

    Article  PubMed  CAS  Google Scholar 

  6. Mazzola JL, Sirover MA. Alteration of intracellular structure and function of glyceraldehyde-3-phosphate dehydrogenase: a common phenotype of neurodegenerative disorders? Neurotoxicology. 2002;23:603–9.

    Article  PubMed  CAS  Google Scholar 

  7. Shulze H, Schuyler A, Stuber D, Dobeli H, Langen H, Huber G. Rat brain glyceraldehyde-3-phosphate dehydrogenase interacts with the recombinant cytoplasmic domain of Alzheimer’s β-amyloid precursor protein. J Neurochem. 1993;60:1915–22.

    Article  Google Scholar 

  8. Oyama R, Yamamoto H, Titani K. Glutamine synthetase, hemoglobin K-chain, and macrophage migration inhibitory factor binding to amyloid l-protein: their identification in rat brain by a novel affinity chromatography and in Alzheimer’s disease brain by immunoprecipitation. Biochim Biophys Acta. 2000;1479:91–102.

    Article  PubMed  CAS  Google Scholar 

  9. Verdier Y, Huszar E, et al. Identification of synaptic plasma membrane proteins co-precipitated with fibrillar β-amyloid peptide. J Neurochem. 2005;94:617–28.

    Article  PubMed  CAS  Google Scholar 

  10. Verdier Y, Foldi I, Sergeant N, Fulop L, Penke Z, Janaky T, Szucs M, Penke B. Characterization of the interaction between Aβ 1–42 and glyceraldehyde-3- phosphate dehydrogenase. J Pept Sci. 2008;14:755–62.

    Article  PubMed  CAS  Google Scholar 

  11. Burke JR, Enghild JJ, Martin ME, Jou Y-S, Myers RM, Roses AD, Vance JM, Strittmatter WJ. Huntingtin and DRPLA proteins selectively interact with the enzyme GAPDH. Nat Med. 1996;2:347–50.

    Article  PubMed  CAS  Google Scholar 

  12. Bae BI, Hara MR, Cascio MB, Wellington CL, Hayden MR, Ross CA, Ha HC, Li X- J, Snyder SH, Sawa A. Mutant huntingtin: nuclear translocation and cytotoxicity mediated by GAPDH. Proc Natl Acad Sci USA. 2006;103:3405–9.

    Article  PubMed  CAS  Google Scholar 

  13. Koshy B, Matilla T, Burright EN, Merry DE, Fischbeck KH, Orr HT, Zoghbi HY. Spinocerebellar ataxia type-1 and spinobulbar muscular atrophy gene products interact with glyceraldehyde-3-phosphate dehydrogenase. Hum Mol Genet. 1996;5:1311–8.

    Article  PubMed  CAS  Google Scholar 

  14. Tatton NA. Increased caspase 3 and Bax immunoreactivity accompany nuclear GAPDH translocation and neuronal apoptosis in Parkinson’s disease. Exp Neurol. 2000;166:29–43.

    Article  PubMed  CAS  Google Scholar 

  15. Kragten E, Lalande I, Zimmerman K, Roggo S, Schindler P, Muller D, van Oostrum J, Waldmeier P, Furst P. Glyceraldehyde-3-phosphate dehydrogenase, the putative target of the antiapoptotic compounds CGP 3466 and R-(−)deprenyl. J Biol Chem. 1998;273:5821–8.

    Article  PubMed  CAS  Google Scholar 

  16. Maruyama W, Akao Y, Youdim MBH, Davis BA, Naoi M. Transfection- enforced Bcl-2 over-expression and an anti-Parkinson drug, rasagiline, prevent nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase induced by an endogeneous dopaminergic neurotoxin, N-methyl(R)salsolinol. J Neurochem. 2001;78:727–35.

    Article  PubMed  CAS  Google Scholar 

  17. Ling Y, Morgan K, Kalsheker N. Amyloid precursor protein (APP) and the biology of proteolytic processing: relevance to Alzheimer’s disease. Int J Biochem Cell Biol. 2003;35:1505–35.

    Article  PubMed  CAS  Google Scholar 

  18. Walsh DM, Selkoe DJ. Aβ Oligomers—a decade of discovery. J Neurochem. 2007;101:1172–84.

    Article  PubMed  CAS  Google Scholar 

  19. Yanker BA, Lu T. Amyloid β-protein toxicity and the pathogenesis of Alzheimer disease. J Biol Chem. 2009;284:4755–9.

    Article  Google Scholar 

  20. Connor JR, Menzies SL, St. Martin SM, Mufson EJ. A histochemical study of iron, transferrin and ferritin in Alzheimer’s diseased brain. J Neurosci Res. 1992;31:75–83.

    Article  PubMed  CAS  Google Scholar 

  21. Connor JR, Snyder BS, Beard JL, Fine RE, Mufson EJ. Regional distribution of iron and iron-regulatory proteins in the brain in aging and Alzheimer’s disease. J Neuorsci Res. 1992;31:327–35.

    Article  CAS  Google Scholar 

  22. Smith MA, Harris PLR, Sayre L, Perry G. Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. Proc Natl Acad Sci USA. 1997;94:9866–8.

    Article  PubMed  CAS  Google Scholar 

  23. Rival T, Page RM, et al. Fenton chemistry and oxidative stress mediate the toxicity of the β-amyloid peptide in a Drosophila model of Alzheimer’s disease. Eur J Neurosci. 2009;29:1335–47.

    Article  PubMed  Google Scholar 

  24. Jomova K, Vondrakova D, Lawson M, Valko M. Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem. 2010;345:91–104.

    Article  PubMed  CAS  Google Scholar 

  25. Zheng I, Roeder RG, Luo Y. S phase activation of the histone H2B promoter by OCA-S, a coactivator complex that contains GAPDH as a key component. Cell. 2003;114:255–66.

    Article  PubMed  CAS  Google Scholar 

  26. Tisdale EJ. Glyceraldehyde-3-phosphate dehydrogenase is required for vesicular transport in the early secretory pathway. J Biol Chem. 2001;276:2480–6.

    Article  PubMed  CAS  Google Scholar 

  27. Tisdale EJ. Glyceraldehyde-3-phosphate dehydrogenase is phosphorylated by protein kinase Cί/λ and plays a role in microtubule dynamics in the early secretory pathway. J Biol Chem. 2002;277:3334–41.

    Article  PubMed  CAS  Google Scholar 

  28. Tisdale EJ, Artalejo CR. Src-dependent aprotein kinase C ί/λ (aPKCί/λ) tyrosine phosphorylation is required for aPKCί/λ association with Rab2 and glyceraldehyde-3-phosphate dehydrogenase on pre-golgi intermediates. J Biol Chem. 2006;281:8436–42.

    Article  PubMed  CAS  Google Scholar 

  29. Tisdale EJ, Azizi F, Artalejo CR. Rab2 utilizes glyceraldehyde-3-phosphate dehydrogenase and protein kinase Cί to associate with microtubules and to recruit dynein. J Biol Chem. 2009;284:5876–84.

    Article  PubMed  CAS  Google Scholar 

  30. Harada N, Yasunaga R, Higashimura Y, Yamaji R, Fujimoto K, Moss J, Inui H, Nakano Y. Glyceraldehyde-3-phosphate dehydrogenase enhances transcriptional activity of androgen receptor in prostate cancer cells. J Biol Chem. 2007;282:22651–61.

    Article  PubMed  CAS  Google Scholar 

  31. Raje CI, Kumar S, Harle A, Nanda JS, Raje M. The macrophage cell surface glyceraldehyde-3-phosphate dehydrogenase is a novel transferrin receptor. J Biol Chem. 2007;282:3252–61.

    Article  PubMed  CAS  Google Scholar 

  32. Azam S, Jouvet N, Jilani A, Vongsamphanh R, Yang X, Yang S, Ramotar D. Human glyceraldehyde-3-phosphate dehydrogenase plays a direct role in reactivating oxidized forms of the DNA repair enzyme APE1. J Biol Chem. 2008;283:30632–41.

    Article  PubMed  CAS  Google Scholar 

  33. Sundararaj KP, Wood RE, Ponnusamy S, Salas AM, Szulc Z, Bielawska A, Obeid LM, Hannun YA, Ogretmen B. Rapid shortening of telomere length in response to ceramide involves the inhibition of telomere binding activity of nuclear glyceraldehyde-3-phosphate dehydrogenase. J Biol Chem. 2004;279:6152–62.

    Article  PubMed  CAS  Google Scholar 

  34. Demarse NA, Ponnusamy S, Spicer EK, Apohan E, Baatz JE, Ogretman B, Davies C. Direct binding of glyceraldehyde-3-phosphate dehydrogenase to telomeric DNA protects telomeres against chemotherapy-induced rapid degradation. J Mol Biol. 2009;394:789–803.

    Article  PubMed  CAS  Google Scholar 

  35. Bonafe N, Gilmore-Hebert M, Folk NL, Azodi M, Zhou Y, Chambers SK. Glyceraldehyde-3-phosphate dehydrogenase binds to the AU-rich 3′untranslated region of colony-stimulating factor-1 (CSF-1) messenger RNA in human ovarian cancer cells: possible role of CSF-1 posttranscriptional regulation and tumor phenotype. Cancer Res. 2005;65:3762–71.

    Article  PubMed  CAS  Google Scholar 

  36. Zhou Y, Yi X, Stofffer JB, Bonafe N, Gilmore-Hebert M, McAlpine J, Chambers SK. The multifunctional protein glyceraldehyde-3-phosphate dehydrogenase is both regulated and controls colony-stimulating factor-1 messenger RNA stability in ovarian cancer. Mol Cancer Res. 2008;6:1375–80.

    Article  PubMed  CAS  Google Scholar 

  37. Rodriguex-Pascual F, Redondo-Horcajo M, Magan-Marchal N, Lagares D, Martinez- Ruiz A, Kleinert H, Lamas S. Glyceraldehyde-3-phosphate dehydrogenase regulates endothelin-1 expression by a novel, redox-sensitive mechanism involving mRNA stability. Mol Cell Biol. 2008;28:7139–55.

    Article  Google Scholar 

  38. Backlund M, Paukku K, Daviet L, De Boer RA, Valo E, Hautaniemi S, Kalkkinen N, Ehsan A, Kontula KK, Lehtonen JA. Posttranscriptional regulation of angiotensin II type 1 receptor expression by glyceraldehyde-3-phosphate dehydrogenase. NucleicAcids Res. 2009;37:2346–235.

    Article  CAS  Google Scholar 

  39. Dunn LL, Rahmanto YS, Richardson DR. Iron uptake and metabolism in the new millennium. Trends Cell Biol. 2007;17:93–100.

    Article  PubMed  CAS  Google Scholar 

  40. Winterbourn CC. Toxicity of iron and hydrogen peroxide: the Fenton reaction. Toxicol Lett. 1995;82:969–74.

    Article  PubMed  Google Scholar 

  41. Fuchs H, Lucken U, Tauber R, Engel A, Geβner R. Structural model of phospholipid-reconstituted human transferrin receptor derived by electron microscopy. Structure. 1998;6:1235–43.

    Article  PubMed  CAS  Google Scholar 

  42. Aisen P. Transferrin receptor 1. Int J Biochem Cell Biol. 2004;36:2137–43. Raje.

    Article  PubMed  CAS  Google Scholar 

  43. Kumar S, Sheokand N, Mhadeshwar MA, Raje CI, Rage M. Characterization of glyceraldehyde-3-phosphate dehydrogenase as a novel transferrin receptor. Int J Biochem Cell Biol. 2012;44:189–99.

    Article  PubMed  CAS  Google Scholar 

  44. Robbins AR, Ward RD, Oliver C. A mutation in glyceraldehyde-3-phosphate dehydrogenase alters endocytosis in CHO cells. J Cell Biol. 1995;130:1093–104.

    Article  PubMed  CAS  Google Scholar 

  45. Pietrini P, Alexander GE, Furey ML, Hampel H, Guazzelli M. The neurometabolic landscape of cognitive decline: in vivo studies with positron emission tomography in Alzheimer’s disease. Int J Psychophysiol. 2000;37:87–98.

    Article  PubMed  CAS  Google Scholar 

  46. Dodart JC, Mathisa C, Bales KR, Paul SM, Ungerera A. Early regional cerebral glucose hypometabolism in transgenic mice overexpressing the V717F b- amyloid precursor protein. Neurosci Lett. 1999;277:49–52.

    Article  PubMed  CAS  Google Scholar 

  47. Meier-Ruge W, Bertoni-Freddari C. The significance of glucose turnover in the brain in the pathogenic mechanisms of Alzheimer’s disease. Rev Neurosci. 1996;7:1–19.

    Article  PubMed  CAS  Google Scholar 

  48. Mazzola JL, Sirover MA. Reduction of glyceraldehyde-3-phosphate dehydrogenase activity in Alzheimer’s disease and Huntington’s disease fibroblasts. J Neurochem. 2001;76:442–9.

    Article  PubMed  CAS  Google Scholar 

  49. Mazzola JL, Sirover MA. Subcellular alteration of glyceraldehyde-3-phosphate dehydrogenase in Alzheimer’s disease fibroblasts. J Neurosci Res. 2003;71:279–85.

    Article  PubMed  CAS  Google Scholar 

  50. Mazzola JL, Sirover MA. Subcellular analysis of aberrant protein structure in age-related neurodegenerative disorders. J Neurosci Methods. 2004;137:241–6.

    Article  PubMed  CAS  Google Scholar 

  51. Cumming RC, Schubert D. Amyloid-β induces disulfide bonding and aggregation of GAPDH in Alzheimer’s disease. FASEB J. 2005;19:2060–2.

    PubMed  CAS  Google Scholar 

  52. Shalova IN, Cechalova K, et al. Decrease of dehydrogenase activity of dehydrogenase activity of cerebral glyceraldehydes-3-phosphate dehydrogenase in different animal models of Alzheimer’s disease. Biochim Biophys Acta. 2007;1770:826–32.

    Article  PubMed  CAS  Google Scholar 

  53. Naletova I, Schmalhausen E, Kharitonov A, Katrukha A, Saso L, Caprioli A, Muronetz V. Non-native glyceraldehyde-3-phosphate dehydrogenase can be an intrinsic component of amyloid structures. Biochim Biophys Acta. 2008;1784:2052–8.

    Article  PubMed  CAS  Google Scholar 

  54. Glaser PE, Gross RW. Rapid plasmenylethanolamine-selective fusion of membrane bilayers catalyzed by an isoform of glyceraldehyde-3 phosphate dehydrogenase: discrimination between glycolytic and fusogenic roles of individual isoforms. Biochemistry. 1995;34:12194–203.

    Article  Google Scholar 

  55. Selkoe DJ. Alzheimer’s disease is a synaptic failure. Science. 2002;298:789–91.

    Article  PubMed  CAS  Google Scholar 

  56. Wu K, Aoki C, Else A, Rogalski-Wilk AA, Siekevtz P. The synthesis of ATP by glycolytic enzymes in the postsynaptic density and the effect of endogenously generated nitric oxide. Proc Natl Acad Sci USA. 1997;94:13273–8.

    Article  PubMed  CAS  Google Scholar 

  57. Laschet JJ, Minier F, et al. Glyceraldehyde-3-phosphate dehydrogenase is a GABAA receptor kinase linking glycolysis to neuronal inhibition. J Neurosci. 2004;24:7614–22.

    Article  PubMed  CAS  Google Scholar 

  58. Kornberg MD, Sen N, Hara MR, Juluri KR, Nguyen JVK, Snowman AM, Law L, Hester LD, Snyder SH. GAPDH mediates nitrosylation of nuclear proteins. Nat Cell Biol. 2010;12:1094–100.

    Article  PubMed  CAS  Google Scholar 

  59. Stamler JS, Hess DT. Nascent nitrosylases. Nat Cell Biol. 2010;12:1024–6.

    Article  PubMed  CAS  Google Scholar 

  60. Chakravarti R, Aulak KS, Fox PL, Stuehr DJ. GAPDH regulates cellular heme insertion into inducible nitric oxide synthase. Proc Natl Acad Sci USA. 2010;107:18004–9.

    Article  PubMed  CAS  Google Scholar 

  61. Butterfield DA, Hardas SS, Bader Lange ML. Oxidatively modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and Alzheimer’s disease: many pathways to neurodegeneration. J Alzheimers Dis. 2010;20:369–93.

    PubMed  CAS  Google Scholar 

  62. Boyd-Kimball D, Sultana R, et al. Proteomic identification of proteins specifically oxidized by intracerebral injection of amyloid β-peptide (1–42) into rat brain: Implications for Alzheimer’s disease. Neuroscience. 2005;132:313–24.

    Article  PubMed  CAS  Google Scholar 

  63. Sultana R, Newman SF, et al. Protective effect of D609 against amyloid- beta1-42-inducded oxidative modification of neuronal proteins: redox proteomics study. J Neurosci Res. 2006;84:409–17.

    Article  PubMed  CAS  Google Scholar 

  64. Nakajima H, Amano W, et al. The active site cysteine of the proapoptotic protein glyceraldehyde-3-phosphate dehydrogenase is essential in oxidative stress-induced aggregation and cell death. J Biol Chem. 2007;282:26562–74.

    Article  PubMed  CAS  Google Scholar 

  65. Hara MR, Agrawal N, et al. S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding. Nat Cell Biol. 2005;7:665–74.

    Article  PubMed  CAS  Google Scholar 

  66. Hara MR, Snyder SH. Nitric oxide-GAPDH-siah: a novel cell death cascade. Cell Mol Neurobiol. 2006;26:525–36.

    Article  Google Scholar 

  67. Hara MR, Cascio MB, Sawa A. GAPDH as a sensor of NO stress. Biochim Biophys Acta. 2006;1762:502–9.

    Article  PubMed  CAS  Google Scholar 

  68. Sen N, Hara MR, et al. Nitric oxide-induced nuclear GAPDH activates p300/CBP and mediates apoptosis. Nat Cell Biol. 2008;10:866–73.

    Article  PubMed  CAS  Google Scholar 

  69. Yego ECK, Vincent JA, Sarthy VP, Busik I, Mohr S. Differential regulation of high glucose-induced glyceraldehyde-3-phosphate dehydrogenase nuclear accumulation in muller cells by IL-1beta and IL-6. Invest Opthalmol Vis Sci. 2009;50:1920–8.

    Article  Google Scholar 

  70. Yego ECK, Mohr S. Siah-1 protein is necessary for high glucose-induced glyceraldehyde-3-phosphate dehydrogenase nuclear accumulation and cell death in muller cells. J Biol Chem. 2010;285:3181–90.

    Article  PubMed  CAS  Google Scholar 

  71. Colell A, Ricci JE, et al. GAPDH and autophagy preserve survival after cytochrome c release in the absence of caspase activation. Cell. 2007;129:983–97.

    Article  PubMed  CAS  Google Scholar 

  72. Colell S, Green DR, Ricci JE. Novel roles for GAPDH in cell death and carcinogenesis. Cell Death Differ. 2009;16:1573–81.

    Article  PubMed  CAS  Google Scholar 

  73. Townsend KP, Obregon D, Quadros A, Patel N, Volmer CH, Paris D, Mullan M. Proinflammatory and vasoactive effects of Aβ in the cerebrovasculature. Ann N Y Acad Sci. 2002;977:65–76.

    Article  PubMed  CAS  Google Scholar 

  74. Iadecola C. Cerebrovascular effects of amyloid-β peptides: mechanisms and implications for Alzheimer’s dementia. Cell Mol Neurobiol. 2003;23:681–9.

    Article  PubMed  CAS  Google Scholar 

  75. Puder M, Soberman RJ. Glutathione conjugates recognize the Rossmann fold of glyceraldehyde-3-phosphate dehydrogenase. J Biol Chem. 1997;272:10936–40.

    Article  PubMed  CAS  Google Scholar 

  76. Albakri QA, Stuehr DJ. Intracellular assembly of inducible NO synthase is limited by nitric oxide-mediated changes in heme insertion and availability. J Biol Chem. 1996;271:5414–21.

    Article  PubMed  CAS  Google Scholar 

  77. Chakravarti R, Stuehr DJ. Thioredoxin-1 regulates cellular heme insertion by controlling S-nitrosation of glyceraldehyde-3-phosphate dehydrogenase. J Biol Chem. 2012;287:16179–86.

    Article  PubMed  CAS  Google Scholar 

  78. Koo EH, Squazzo SL. Evidence that production and release of amyloid β- protein involves the endocytic pathway. J Biol Chem. 1994;269:17386–9.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgment

Work in the author’s laboratory was funded by a grant from the National Institutes of Health (CA 119285).

Note Added in Proof A recent study reported the intriguing finding that GAPDH may be secreted externally to “search and locate” Fe++ for intracellular transport and metabolism. (Sheokand et al., Secreted glyceraldehyde-3-phosphate dehydrogenase is a multifunctional autocrine transferrin receptor for cellular iron acquisition, Biochim Biophys Acta, 1830, 3818–3827, 2013). The latter emphasizes further the role of GAPDH in cellular Fe++ function.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, 19140, USA

    Michael A. Sirover Ph.D.

Authors
  1. Michael A. Sirover Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael A. Sirover Ph.D. .

Editor information

Editors and Affiliations

  1. Pharmacology, Temple University, Philadelphia, Pennsylvania, USA

    Domenico Praticὸ

  2. Istituto di Gerontologia e Geriatria, Università degli Studi di Perugia, Perugia, Italy

    Patrizia Mecocci

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Sirover, M.A. (2013). GAPDH: β-Amyloid Mediated Iron Accumulation in Alzheimer’s Disease: A New Paradigm for Oxidative Stress Induction in Neurodegenerative Disorders. In: Praticὸ, D., Mecocci, P. (eds) Studies on Alzheimer's Disease. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-598-9_4

Download citation

Publish with us

Policies and ethics

Search

Navigation