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Ongoing Studies of Deimination in Neurodegenerative Diseases Using the F95 Antibody

  • Anthony P. Nicholas
  • Liang Lu
  • Michael Heaven
  • Inga Kadish
  • Thomas van Groen
  • Mary Ann Accaviti-Loper
  • Sonja Wewering
  • Diane Kofskey
  • Pierluigi Gambetti
  • Michael Brenner
Chapter

Abstract

Over the past decade, growing evidence has emerged, suggesting that protein deimination is increased in human neurodegenerative disorders such as Alzheimer's disease, Creutzfeldt–Jakob disease, and Parkinson's disease. As an additional tool to identify affected proteins, some of these experiments utilized the F95 monoclonal antibody, which can theoretically recognize any protein in which arginine amino acids have been transformed to citrullines. This chapter outlines previous studies of brain protein deimination in these aforementioned maladies using F95 as well as ongoing unpublished studies of other neurodegenerative disorders such as Alexander's disease, amyotrophic lateral sclerosis, diffuse Lewy body disease, some primary astrocytic neoplasms, and normal brain aging. In addition, some data associated with the animal models of these conditions are also presented. Collectively, most of these conditions support the trending concept that neurodegeneration, for whatever reason, is accompanied by amplified citrullination, although the proteins affected and pattern of increased deimination in the central nervous system may differ in different disease states.

Keywords

Aging Alexander disease Alzheimer’s disease Amyotrophic lateral sclerosis Creutzfeldt–Jakob disease Diffuse Lewy body disease Glioma Parkinson’s disease 

Notes

Acknowledgements

These experiments were supported by the Research Program of the Department of Veterans Health Administration and grants from the Parkinson Association of Alabama, The Strain Family Foundation, and an MREP Award from the Department of Veterans Affairs. MB and MH were supported by NIH grant P01NS42803. We also would like to thank Deborah Freemen, Joshua D. Echols, Jeffery L. King, Kiran B. Gupta, Carey McInnis, William W. Snow, Sapan Majmundar, Padmapriya Vattem, Dr. Thiagarajan Sambandam, and Dr. Christopher C. Gelwix for technical assistance.

In addition, we also gratefully acknowledge the numerous sources of human brain specimens, including Dr. Francine M Benes of the Harvard Brain Tissue Resource Center, which is supported in part by PHS grant number MH/NS 31862; Dr. H. Ronald Zielke of the Brain and Tissue Bank for Developmental Disorders at the University of Maryland in Baltimore; Dr. William W. Tourtellotte of the National Neurological Research Specimen Bank, VAMC, in Los Angeles, which is sponsored by NINDS/NIMH, National Multiple Sclerosis Society, VA Greater Los Angeles Healthcare System, and Veterans Health Services and Research Administration, Department of Veterans Affairs; and Drs. Steven Carroll and Richard Powers of the Alzheimer’s Disease Research Center Neuropathology Core and the Brain Resource Program at the University of Alabama at Birmingham, which were sponsored in part by National Institutes of Health, grant numbers P50 AG016582, NP30 NS57098, and P30 NS47466. Finally, we would also like to specifically thank Dr. Yancey Gillespie, for providing human astrocytic tumor specimens, and the Pathology Department of the University of Alabama at Birmingham, for glioma samples and spinal cords from ALS and control patients.

References

  1. Acharya NK, Nagele EP, Han M, Coretti NJ, Demarshall C, Kosciuk MC et al (2012) Neuronal PAD4 expression and protein citrullination: possible role in production of autoantibodies associated with neurodegenerative disease. J Autoimmun 38:369–380PubMedCrossRefGoogle Scholar
  2. Akiyama H, Schwab C, Kondo H, Mori H, Kametani F, Ikeda K et al (1996) Granules in glial cells of patients with Alzheimer’s disease are immunopositive for C-terminal sequences of β-amyloid protein. Neurosci Lett 206:169–172PubMedCrossRefGoogle Scholar
  3. Akiyama K, Sakurai Y, Asou H, Senshu T (1999) Localization of peptidylarginine deiminase type II in a stage-specific immature oligodendrocyte from rat cerebral hemisphere. Neurosci Lett 274:53–55PubMedCrossRefGoogle Scholar
  4. Andrew SM, Titus JA, Coico R, Amin A (1997) Purification of immunoglobulin M and immunoglobulin D. Curr Protoc Immunol 21(Suppl):2.9.1–2.9.8Google Scholar
  5. Bhattacharya SK (2009) Retinal deimination in aging and disease. IUBMB Life 61:504–509PubMedCrossRefGoogle Scholar
  6. Borchelt DR, Thinakaran G, Eckman CB, Lee MK, Davenport F, Ratovitsky T et al (1996) Familial Alzheimer’s disease-linked presenilin 1 variants elevate Aβ1-42/1-40 ratio in vitro and in vivo. Neuron 17:1005–1013PubMedCrossRefGoogle Scholar
  7. Brenner M, Johnson AB, Boespflug-Tanguy O, Rodriguez D, Goldman JE, Messing A (2001) Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. Nat Genet 27:117–120PubMedCrossRefGoogle Scholar
  8. Chang X, Han J (2006) Expression of peptidylarginine deiminase type 4 (PAD4) in various tumors. Mol Carcinog 45:183–196PubMedCrossRefGoogle Scholar
  9. De Rycke L, Nicholas AP, Cantaert T, Kruithof E, Echols JD, Vandekerckhove B et al (2005) Synovial intracellular citrullinated proteins colocalizing with peptidyl arginine deiminase are pathophysiologically relevant antigenic determinants of rheumatoid arthritis-specific humoral autoimmunity. Arthritis Rheum 52:2323–2330PubMedCrossRefGoogle Scholar
  10. Eriksen JL, Dawson TM, Dickson DW, Petrucelli L (2003) Caught in the act: α-synuclein is the culprit in Parkinson’s disease. Neuron 40:453–456PubMedCrossRefGoogle Scholar
  11. Frautschy SA, Cole GM, Baird A (1992) Phagocytosis and deposition of vascular beta-amyloid in rat brains injected with Alzheimer beta-amyloid. Am J Pathol 140:1389–1399PubMedGoogle Scholar
  12. Grant JE, Hu J, Liu T, Jain MR, Elkabes S, Li H (2007) Post-translational modifications in the rat lumbar spinal cord in experimental autoimmune encephalomyelitis. J Proteome Res 6:2786–2791PubMedCrossRefGoogle Scholar
  13. Harauz G, Musse AA (2007) A tale of two citrullines—structural and functional aspects of myelin basic protein deimination in health and disease. Neurochem Res 32:137–158PubMedCrossRefGoogle Scholar
  14. Harlow E, Lane DP (1988) Antibodies: a laboratory manual. Cold Spring Harbor Publishing, New YorkGoogle Scholar
  15. Ishigami A, Ohsawa T, Hiratsuka M, Taguchi H, Kobayashi S, Saito Y et al (2005) Abnormal accumulation of citrullinated proteins catalyzed by peptidylarginine deiminase in hippocampal extracts from patients with Alzheimer’s disease. J Neurosci Res 80:120–128PubMedCrossRefGoogle Scholar
  16. Jang B, Jin JK, Jeon YC, Cho HJ, Ishigami A, Choi KC et al (2010) Involvement of peptidylarginine deiminase-mediated post-translational citrullination in pathogenesis of sporadic Creutzfeldt-Jakob disease. Acta Neuropathol 119:199–210PubMedCrossRefGoogle Scholar
  17. Keilhoff G, Prell T, Langnaese K, Mawrin C, Simon M, Fansa H et al (2008) Expression pattern of peptidylarginine deiminase in rat and human Schwann cells. Dev Neurobiol 68:101–114PubMedCrossRefGoogle Scholar
  18. Liu L, Ikonen S, Heikkinen T, Tapiola T, van Groen T, Tanila H (2002) The effects of long-term treatment with metrifonate, a cholinesterase inhibitor, on cholinergic activity, amyloid pathology, and cognitive function in APP and PS1 doubly transgenic mice. Exp Neurol 173:196–204PubMedCrossRefGoogle Scholar
  19. Lu L, Wang S, Zheng L, Li X, Suswam EA, Zhang X et al (2009) Amyotrophic lateral sclerosis-linked mutant SOD1 sequesters Hu antigen R (HuR) and TIA-1-related protein (TIAR): implications for impaired post-transcriptional regulation of vascular endothelial growth factor. J Biol Chem 284:33989–33998PubMedCrossRefGoogle Scholar
  20. Ludolph AC, Brettschneider J, Weishaupt JH (2012) Amyotrophic lateral sclerosis. Curr Opin Neurol 25:530–535PubMedCrossRefGoogle Scholar
  21. Mendritzki S, Schmidt S, Sczepan T, Zhu XR, Segelcke D, Lübbert H (2010) Spinal cord pathology in alpha-synuclein transgenic mice. Parkinsons Dis 2010:375462PubMedGoogle Scholar
  22. Messing A, Head MW, Galles K, Galbreath EJ, Goldman JE, Brenner M (1998) Fatal encephalopathy with astrocyte inclusions in GFAP transgenic mice. Am J Pathol 152:391–398PubMedGoogle Scholar
  23. Morren JA, Galvez-Jimenez N (2012) Current and prospective disease-modifying therapies for amyotrophic lateral sclerosis. Expert Opin Investig Drugs 21:297–320PubMedCrossRefGoogle Scholar
  24. Moscarello MA, Wood DD, Ackerly C, Boulias C (1994) Myelin in multiple sclerosis is developmentally immature. J Clin Invest 94:146–154PubMedCrossRefGoogle Scholar
  25. Nevens JR, Mallia AK, Wendt MW, Smith PK (1992) Affinity chromatographic purification of immunoglobulin M antibodies utilizing immobilized mannan binding protein. J Chromatogr 597:247–256PubMedCrossRefGoogle Scholar
  26. Nicholas AP (2011) Dual immunofluorescence study of citrullinated proteins in Parkinson diseased substantia nigra. Neurosci Lett 495:26–29PubMedCrossRefGoogle Scholar
  27. Nicholas AP (2013) Dual immunofluorescence study of citrullinated proteins in Alzheimer diseased frontal cortex. Neurosci Lett 545:107–111PubMedCrossRefGoogle Scholar
  28. Nicholas AP, Whitaker JN (2002) Preparation of a monoclonal antibody to citrullinated epitopes: its characterization and some applications to immunohistochemistry in human brain. Glia 37:328–336PubMedCrossRefGoogle Scholar
  29. Nicholas AP, King JL, Sambandam T, Echols JD, Gupta KB, McInnis C et al (2003) Immunohistochemical localization of citrullinated proteins in adult rat brain. J Comp Neurol 459:251–266PubMedCrossRefGoogle Scholar
  30. Nicholas AP, Sambandam T, Echols JD, Tourtellotte WW (2004) Increased citrullinated glial fibrillary acidic protein in secondary progressive multiple sclerosis. J Comp Neurol 473:128–136PubMedCrossRefGoogle Scholar
  31. Nicholas AP, Sambandam T, Echols JD, Barnum SR (2005) Expression of citrullinated proteins in murine experimental autoimmune encephalomyelitis. J Comp Neurol 486:254–266PubMedCrossRefGoogle Scholar
  32. Perng MD, Su M, Wen SF, Li R, Gibbon T, Prescott AR et al (2006) The Alexander disease-causing glial fibrillary acidic protein mutant, R416W, accumulates into Rosenthal fibers by a pathway that involves filament aggregation and the association of αB-crystallin and HSP27. Am J Hum Genet 79:197–213CrossRefGoogle Scholar
  33. Sambandam T, Belousova M, Accavitti-Loper MA, Blanquicett C, Guercello V, Raijmakers R et al (2004) Increased peptidylarginine deiminase type II in hypoxic astrocytes. Biochem Biophys Res Commun 325:1324–1329PubMedCrossRefGoogle Scholar
  34. Shimada N, Handa S, Uchida Y, Fukuda M, Maruyama N, Asaga H et al (2010) Developmental and age-related changes of peptidylarginine deiminase 2 in the mouse brain. J Neurosci Res 88:798–806PubMedGoogle Scholar
  35. van Groen T, Kiliaan AJ, Kadish I (2006) Deposition of mouse amyloid β in human APP/PS1 double and single AD model transgenic mice. Neurobiol Dis 23:653–662PubMedCrossRefGoogle Scholar
  36. Van Langenhove T, van der Zee J, Van Broeckhoven C (2012) The molecular basis of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum. Ann Med 44:817–828PubMedCrossRefGoogle Scholar
  37. Vincent SR, Leung E, Watanabe K (1992) Immunohistochemical localization of peptidylarginine deiminase in rat brain. J Chem Neuroanat 5:159–168PubMedCrossRefGoogle Scholar
  38. Wegiel J, Wang KC, Tarnawski M, Lach B (2000) Microglia cells are the driving force in fibrillar plaque formation, whereas astrocytes are a leading factor in plaque degradation. Acta Neuropathol 100:356–364PubMedCrossRefGoogle Scholar
  39. Wyss-Coray T, Loike JD, Brionne TC, Lu E, Anankov R, Yan F et al (2003) Adult mouse astrocytes degrade amyloid-beta in vitro and in situ. Nat Med 9:453–457PubMedCrossRefGoogle Scholar
  40. Xu K, Malouf AT, Messing A, Silver J (1999) Glial fibrillary acidic protein is necessary for mature astrocytes to react to beta-amyloid. Glia 25:390–403PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Anthony P. Nicholas
    • 1
  • Liang Lu
    • 1
  • Michael Heaven
    • 2
  • Inga Kadish
    • 3
  • Thomas van Groen
    • 3
  • Mary Ann Accaviti-Loper
    • 4
  • Sonja Wewering
    • 5
  • Diane Kofskey
    • 6
  • Pierluigi Gambetti
    • 6
  • Michael Brenner
    • 7
  1. 1.Department of NeurologyUniversity of Alabama at Birmingham and the Birmingham Veterans Administration Medical CenterBirminghamUSA
  2. 2.Department of Biochemistry and Molecular GeneticsUniversity of Alabama at BirminghamBirminghamUSA
  3. 3.Department of Cell BiologyUniversity of Alabama at BirminghamBirminghamUSA
  4. 4.Department of MedicineUniversity of Alabama at BirminghamBirminghamUSA
  5. 5.Department of Animal PhysiologyRuhr-University BochumBochumGermany
  6. 6.National Prion Disease Pathology Surveillance Center, Institute of PathologyCase Western Reserve UniversityClevelandUSA
  7. 7.Department of NeurobiologyUniversity of Alabama at BirminghamBirminghamUSA

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