Introduction

Chapter 1. Adult Neurogenesis in Etiology and Pathogenesis of Alzheimer’s Disease

Chapter 2. Adult Neurogenesis and Aneuploidy in Etiology, Pathogenesis and Pathology of Alzheimer’s Disease

Chapter 3. Adult Neurogenesis, Neural Stem Cells and Alzheimer’s Disease: Developments, Limitations, Problems and Promises

Chapter 4. Oxidative Stress in Adult Neurogenesis and in the Pathogenesis of Alzheimer's Disease

Chapter 5. Adult Neurogenesis, Neuroinflamation, and Therapeutic Potential of Adult Neural Stem Cells

Chapter 6. Adult Neurogenesis and Drug Therapy

Chapter 7. Neurogenesis and the Effect of Antidepressants

Chapter 8. Neurogenic Drugs and Compounds to Treat CNS Diseases and Disorders

Chapter 9. Patent Evaluation. Thirteen Compounds Promoting Oligodendrocyte Progenitor Cell Differentiation and Remyelination for Treating Multiple Sclerosis: Wo2010054307

Chapter 10. Patent Evaluation. Antibodies against CD20 (Rituximab) for Treating Multiple Sclerosis: US20100233121

Chapter 11. Umbilical Cord Blood and Alpha-3 Fucosyl Transferase-Treated Haematopoietic Stem Cells for Transplantation

Chapter 12. Patent Evaluation. Cell Lines Expressing Mutant FX Proteins to Generate Proteins with Reduced Rate of Fucosylation: Wo2010/141478

Chapter 13. Patent Evaluation. Modulation of GDP-Fucose Level for Generating Proteins with Reduced Rate of Fucosylation (Wo2010141855)

Chapter 14. Patent Evaluation. Chimeric Proteins Comprising the Constant Region of Immunoglobulins for Treating Haemophilia B (WO2005001025)

Chapter 15. Patent Evaluation Parthenogenetically Activated Human Oocytes and Parthenogenetic Embryonic Stem Cells: US20100233143

Chapter 16. Tuberous Sclerosis Complex: A Paradigm for Studying Adult Neurogenesis and Brain Tumors

Chapter 17. Adult Neurogenesis in Alzheimer’s Disease and Therapies

Chapter 18. Indacaterol for the Treatment of Patients with Moderate-to-Severe COPD

Conclusions

Index

Introduction

[1] Taupin, P. (2006) Neurogenesis in the adult central nervous system. C. R. Biol. 329, 465-475.
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[3] Querfurth, H.W. et al. (2010) Alzheimer’s disease. N. Engl. J. Med. 362, 329-344.
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[5] Yang, Y. et al. (2003) Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer’s disease. J. Neurosci. 23, 2557-2563.
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[9] Li, J. et al. (1997) Alzheimer presenilins in the nuclear membrane, interphase kinetochores, and centrosomes suggest a role in chromosome segregation. Cell 90, 917-927.
[10] Kim, H. et al. (1986) The binding of MAP-2 and tau on brain microtubules in vitro: implications for microtubule structure. Ann. N. Y. Acad. Sci. 466, 218-239.

Chapter 1

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Chapter 2

[1] Ferri, C.P., Prince, M., Brayne, C., Brodaty, H., Fratiglioni, L., Ganguli, M., Hall, K., Hasegawa, K., Hendrie, H., Huang, Y., Jorm, A., Mathers, C., Menezes, P.R., Rimmer, E. and Scazufca, M.; Alzheimer's Disease International. (2005) Global prevalence of dementia: a Delphi consensus study. Lancet, 366, 2112-7.
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[6] Nishimura, M., Yu, G. and St George-Hyslop, P.H. (1999) Biology of presenilins as causative molecules for Alzheimer disease. Clin. Genet., 55, 219-25.
[7] Wang, J.F., Lu, R., and Wang, Y.Z. (2010) Regulation of β cleavage of amyloid precursor protein. Neurosci. Bull., 26, 417-27.
[8] Fukutani, Y., Kobayashi, K., Nakamura, I., Watanabe, K., Isaki, K. and Cairns, N.J. (1995) Neurons, intracellular and extra cellular neurofibrillary tangles in subdivisions of the hippocampal cortex in normal ageing and Alzheimer's disease. Neurosci. Lett., 200, 57-60.
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Chapter 3

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Chapter 4

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Chapter 12

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[3] Upreti RK, Kumar M, Shankar V. Bacterial glycoproteins: functions, biosynthesis and applications. Proteomics 2003;3:363-79.
[4] Taupin P, Ray J, Fischer WH, et al. FGF-2-responsive neural stem cell proliferation requires CCg, a novel autocrine/paracrine cofactor. Neuron 2000;28:385-97.
** The glycosylation of CCg is required for its activity as a neural stem cell factor, co-factor of FGF-2.
[5] Taupin P. Ex vivo fucosylation to improve the engraftment capability and therapeutic potential of human cord blood stem cells. Drug Discovery Today 2010;15:698-9.
[6] Taupin P. Transplantation of cord blood stem cells for treating hematologic diseases and strategies to improve engraftment. Therapy 2010;7:703-15.

** Treatment of cord blood tissue with FTVI, prior transplantation, improves the homing and engraftment of cord blood stem cells to the bone marrow.
[7] Moriwaki K, Miyoshi E. Fucosylation and gastrointestinal cancer. World J Hepatol 2010;2:151-61.
[8] Miyoshi E, Moriwaki K, Nakagawa T. Biological function of fucosylation in cancer biology. J Biochem 2008;143:725-9.
[9] Weninger W, Ulfman LH, Cheng G, et al. Specializedcontributions by a(1,3)-fucosyltransferase-IV and FucT-VII during leukocyte rolling in dermal microvessels. Immunity 2000;12:665-76.
[10] Taupin P. Ex vivo fucosylation of stem cells to improve engraftment: WO2004094619. Expert Opinion on Therapeutic Patents 2010;20:1265-9.
[11] Becker DJ, Lowe JB. Fucose: biosynthesis and biological function in mammals. Glycobiology 2003;13:41R-53R.
** The FX gene is highly conserved in mammals.
[12] Huhn C, Selman MH, Ruhaak LR, et al. IgG glycosylation analysis. Proteomics. 2009;9:882-913.
[13] Taupin P. Antibodies against CD20 (Rituximab) for treating multiple sclerosis: US 20100233121. Expert Opinion on Therapeutic Patents. 2011; 21(1):111-114.
[14] Masuda A, Yoshida M, Shiomi H, et al. Role of Fc Receptors as a therapeutic target. Inflamm Allergy Drug Targets 2009;8:80-6.
[15] Taupin P. Hybrid proteins comprising the constant region of immunoglobulins for treating haemophilia B. Expert Opinion on Therapeutic Patents. 2011; In press.
[16] Jefferis R. Antibody therapeutics: isotype and glycoform selection. Expert Opin Biol Ther. 2007;7:1401-13.

** Antibodies that lack fucosylation can mediate antibody-dependent cell-mediated cytotoxicity better than fucosylated antibodies.
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[19] Malphettes L, Freyvert Y, Chang J, et al. Highly efficient deletion of FUT8 in CHO cell lines using zinc-finger nucleases yields cells that produce completely nonfucosylated antibodies. Biotechnol Bioeng 2010;106:774-83.

Chapter 13

[1] Taupin P, Ray J, Fischer WH, et al. FGF-2-responsive neural stem cell proliferation requires CCg, a novel autocrine/paracrine cofactor. Neuron 2000;28:385-97.

•• The glycosylation of CCg is required for its activity as a neural stem cell factor, co-factor of FGF-2.
[2] Taupin P. Ex vivo fucosylation to improve the engraftment capability and therapeutic potential of human cord blood stem cells. Drug Discovery Today 2010;15:698-9.
[3] Moriwaki K, Miyoshi E. Fucosylation and gastrointestinal cancer. World J Hepatol 2010;2:151-61.
[4] Taupin P. Transplantation of cord blood stem cells for treating hematologic diseases and strategies to improve engraftment. Therapy 2010;7:703-15.

•• Treatment of cord blood tissue with FTVI, prior transplantation, improves the homing and engraftment of cord blood stem cells to the bone marrow.
[5] Moens S, Vanderleyden J. Glycoproteins in prokaryotes. Arch Microbiol 1997;168:169-75.
[6]

••Prokaryotes (Archaea and Bacteria) are able to synthesize glycoproteins.
Hudson JE, Johnson TC. The degradation and turnover of fucosylated glycoproteins in the plasma membrane of a neuroblastoma-cell line. Biochem J 1977;166:217-23.
[7] Jefferis R. Antibody therapeutics: isotype and glycoform selection. Expert Opin Biol Ther. 2007;7:1401-13.
[8] Taupin P. Antibodies against CD20 (Rituximab) for treating multiple sclerosis: US 20100233121. Expert Opinion on Therapeutic Patents. 2011; 21(1):111-114.
[9] Taupin P. Hybrid proteins comprising the constant region of immunoglobulins for treating haemophilia B. Expert Opinion on Therapeutic Patents. 2011; In press.
[10] Miyoshi E, Moriwaki K, Nakagawa T. Biological function of fucosylation in cancer biology. J Biochem 2008;143:725-9.
[11] Taupin P. Ex vivo fucosylation of stem cells to improve engraftment: WO2004094619. Expert Opinion on Therapeutic Patents 2010;20:1265-9.
[12] Bengtson P, Lundblad A, Larson G, et al. Polymorphonuclear leukocytes from individuals carrying the G329A mutation in the 1,3-fucosyltransferase VII gene (FUT7) roll on E- and P-selectins. J Immunol 2002;169:3940-6.
[13] Becker DJ, Lowe JB. Fucose: biosynthesis and biological function in mammals. Glycobiology 2003;13:41R-53R.
[14] Reitman ML, Trowbridge IS, Kornfeld S. Mouse lymphoma cell lines resistant to pea lectin are defective in fucose metabolism. J. Biol Chem 1980;255:9900-6.
[15] Malphettes L, Freyvert Y, Chang J, et al. Highly efficient deletion of FUT8 in CHO cell lines using zinc-finger nucleases yields cells that produce completely nonfucosylated antibodies. Biotechnol Bioeng 2010;106:774-83.
[16] Yurchenco PD, Atkinson PH. Equilibration of fucosyl glycoprotein pools in HeLa cells. Biochemistry 1977;16:944-53.
[17] Yurchenco PD, Atkinson PH. Fucosyl-glycoprotein and precursor polls in HeLa cells. Biochemistry 1975;14:3107-14.

Chapter 14

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•The interaction Fc/FcRn protects IgGs from catabolism and from being marked for degradation.
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[11] Peters RT, Low SC, Kamphaus GD, et al. Prolonged activity of factor IX as a monomeric Fc fusion protein. Blood 2010;115:2057-64.
•• Synthesis and characterization of the hybrid proteins comprising human FIX and the constant region, including the Fc domain, of one or two heavy chain(s) of human IgG (rFIXFc). The half-life of the clotting activity of rFIXFc is 3- to 4-fold longer than that of rFIX.
[12] Lin HF, Maeda N, Smithies O, et al. A coagulation factor IX-deficient mouse model for human hemophilia B. Blood 1997;90:3962-6.
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•• FcRn can be harnessed to noninvasively deliver bioactive proteins into the systemic circulation in therapeutic quantities.
[16] Taupin P. Ex vivo fucosylation of stem cells to improve engraftment: WO2004094619. Expert Opin Ther Pat 2010;20:1265-9.
[17] Taupin P. Transplantation of cord blood stem cells for treating hematologic diseases and strategies to improve engraftment. Therapy 2010;7:703-15.
[18] Taupin P. Antibodies against CD20 (Rituximab) for treating multiple sclerosis: US20100233121. Expert Opin Ther Pat 2011;21:111-4.
[19] Napolitano LM. Scope of the problem: epidemiology of anemia and use of blood transfusions in critical care. Crit Care 2004;8:S1-8.

Chapter 15

[1] Taupin P. Derivation of embryonic stem cells for cellular therapy: Challenges and new strategies. Med Sci Monit 2006;12:RA75-8.
[2] Thomson JA, Kalishman J, Golos TG, et al. Isolation of a primate embryonic stem cell line. Proc Natl Acad Sci USA 1995;92:7844-8.
[3] Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science 1998;282:1145-7. Erratum in: Science 1998;282:1827.
••First report of the derivation and long-term propagation of ESCs from human blastocysyts.
[4] Taupin P. Stem cells engineering for cell-based therapy. J Neur Eng 2007;4:R59-63.
[5] Hao J, Zhu W, Sheng C, et al. Human parthenogenetic embryonic stem cells: one potential resource for cell therapy. Sci China C Life Sci 2009;52:599-602.
[6] Taupin P. Autologous transplantation in the central nervous system. Ind J Med Res 2006;124:613-18.
[7] Pashaiasl M, Khodadadi K, Holland MK, et al. The efficient generation of cell lines from bovine parthenotes. Cell Reprogram 2010;12:571-9.
[8] Sumer H, Liu J, Tat P, et al. Somatic cell nuclear transfer: pros and cons. J Stem Cells 2009;4:85-93.
[9] Shi Y. Induced pluripotent stem cells, new tools for drug discovery and new hope for stem cell therapies. Curr Mol Pharmacol 2009;2:15-8.
[10] Taupin P. Adult neural stem cells, neurogenic niches and cellular therapy. Stem Cell Rev 2006;2:213-19.
[11] Taupin P. Very small embryonic-like stem cells for regenerative medicine: WO2010039241. Exp Opin Ther Patents 2010;20:1103-6.
•Very small embryonic-like stem cells are reported pluripotent stem cells.
[12] Huang J, Okuka M, Wang F, et al. Generation of pluripotent stem cells from eggs of aging mice. Aging Cell 2010;9:113-25.
[13] Brevini TA, Pennarossa G, deEguileor M, et al. Parthenogenetic cell lines: an unstable equilibrium between pluripotency and malignant transformation. Curr Pharm Biotechnol 2011;12:206-12.
•Potential of pESCs for tumor formation.
[14] Taupin P. Stem cells from non-viable versus post-mortem tissues. Med Sci Monit 2007;13:LE1-1
[15] Taupin P. Adult neurogenesis and neural stem cells as a model for the discovery and development of novel drugs. Expert Opinion On Drug Discovery. 2010;5:921-5.
[16] Taupin P. Adult neurogenesis, neural stem cells and Alzheimer’s disease: developments, limitations, problems and promises. Current Alzheimer Research 2009;6:461-70.

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Chapter 17

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Chapter 18

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Conclusion 1

[1] Taupin P, Gage FH: Adult neurogenesis and neural stem cells of the central nervous system in mammals. J. Neurosci Res. 2002; 69(6): 745-749.
[2] Duan X, Kang E, Liu CY, et al.: Development of neural stem cell in the adult brain. Curr Opin Neurobiol. 2008; 18(1): 108-115.
[3] Eriksson PS, Perfilieva E, Bjork-Eriksson T, et al.: Neurogenesis in the adult human hippocampus. Nat Med. 1998; 4(11): 1313-1317.
[4] Curtis MA, Kam M, Nannmark U, et al.: Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science. 2007; 315(5816): 1243-1249.
[5] Taupin P: Adult neural stem cells, neurogenic niches and cellular therapy. Stem Cell Rev. 2006; 2(3): 213-220.
[6] Mitsiadis TA, Barrandon O, Rochat A, et al.: Stem cell niches in mammals. Exp Cell Res. 2007; 313(16): 3377-3385.
[7] Taupin P: Adult neural stem cells from promise to treatment: The road ahead. J Neurodegener Regene. 2008; 1(1): 7-8.
[8] Parent JM, Yu TW, Leibowitz RT, et al.: Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci. 1997; 17(10): 3727-3738.
[9] Gould E, Beylin A, Tanapat P, et al.: Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci. 1999; 2(3): 260-265.
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Conclusion 2

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