Advertisement

Stem Cell Therapies for Neurodegenerative Diseases

  • Kiminobu Sugaya
  • Manjusha Vaidya
Chapter
First Online:
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1056)

Abstract

Stem cell therapies have been proposed as a treatment option for neurodegenerative diseases, but the best stem cell source and therapeutic efficacy for neuroregeneration remain uncertain. Embryonic stem cells (ESCs) and neural stem cells (NSCs), which can efficiently generate neural cells, could be good candidates but they pose ethical and practical issues. Not only difficult to find the good source of those cells but also they alway pose immunorejection problem since they may not be an autologous cells. Even if we overcome the immunorejection problem, it has also been reported that transplantation of ESCs develop teratoma. Although adult stem cells are more accessible, they have a limited developmental potential. We developed technologies to increase potency of mesenchymal stem cells, which allow them to develop into neural cells, by over expression of the ESC gene, nanog. We also developed a small molecule compound, which significantly increases endogenous NSCs by peripheral administration, eliminating even the necessity of stem cell injection to the brain. These novel technologies may offer neuroregenerative therapies for Alzheimers disease (AD). However, we found that AD pathological condition prevent neurogenesis from NSCs. This chapter discusses how to overcome the problem associated stem cell therapy under AD pathology and introduces exosome as a tool to improve the modification of adult stem cells. These new technologies may open a door for the new era for AD therapy.

Keywords

Neural stem cells Embryonic stem cells Alzheimer’s disease Neurodegeneration Parkinson’s disease Octamer 4 Mesenchymal stem cell 
This is a preview of subscription content, log in to check access.

References

  1. 1.
    Siwak-Tapp CT, Head E, Muggenburg BA, Milgram NW, Cotman CW (2007) Neurogenesis decreases with age in the canine hippocampus and correlates with cognitive function. Neurobiol Learn Mem 88(2):249–259PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Wati H, Kudo K, Qiao C, Kuroki T, Kanba S (2006) A decreased survival of proliferated cells in the hippocampus is associated with a decline in spatial memory in aged rats. Neurosci Lett 399(1–2):171–174PubMedCrossRefGoogle Scholar
  3. 3.
    Kadota M, Shirayoshi Y, Oshimura M (2002) Elevated apoptosis in pre-mature neurons differentiated from mouse ES cells containing a single human chromosome 21. Biochem Biophys Res Commun 299(4):599–605PubMedCrossRefGoogle Scholar
  4. 4.
    Wang CC, Kadota M, Nishigaki R, Kazuki Y, Shirayoshi Y, Rogers MS, Gojobori T, Ikeo K, Oshimura M (2004) Molecular hierarchy in neurons differentiated from mouse ES cells containing a single human chromosome 21. Biochem Biophys Res Commun 314(2):335–350PubMedCrossRefGoogle Scholar
  5. 5.
    Zhang C, McNeil E, Dressler L, Siman R (2007) Long-lasting impairment in hippocampal neurogenesis associated with amyloid deposition in a knock-in mouse model of familial Alzheimer’s disease. Exp Neurol 204(1):77–87PubMedCrossRefGoogle Scholar
  6. 6.
    Wolf SA, Kronenberg G, Lehmann K, Blankenship A, Overall R, Staufenbiel M, Kempermann G (2006) Cognitive and physical activity differently modulate disease progression in the amyloid precursor protein (APP)-23 model of Alzheimer’s disease. Biol Psychiatry 60(12):1314–1323PubMedCrossRefGoogle Scholar
  7. 7.
    Rockenstein E, Mante M, Adame A, Crews L, Moessler H, Masliah E (2007) Effects of Cerebrolysin on neurogenesis in an APP transgenic model of Alzheimer’s disease. Acta Neuropathol 113(3):265–275PubMedCrossRefGoogle Scholar
  8. 8.
    Deng YB, Liu XG, Liu ZG, Liu XL, Liu Y, Zhou GQ (2006) Implantation of BM mesenchymal stem cells into injured spinal cord elicits de novo neurogenesis and functional recovery: evidence from a study in rhesus monkeys. Cytotherapy 8(3):210–214PubMedCrossRefGoogle Scholar
  9. 9.
    Qu T, Brannen CL, Kim HM, Sugaya K (2001) Human neural stem cells improve cognitive function of aged brain. Neuroreport 12:1127–1132PubMedCrossRefGoogle Scholar
  10. 10.
    Bizon JL, Gallagher M (2005) More is less: neurogenesis and age-related cognitive decline in Long-Evans rats. Sci Aging Knowl Environ 2005(7):re2CrossRefGoogle Scholar
  11. 11.
    Bizon JL, Lee HJ, Gallagher M (2004) Neurogenesis in a rat model of age-related cognitive decline. Aging Cell 3(4):227–234PubMedCrossRefGoogle Scholar
  12. 12.
    Juengst E, Fossel M (2000) The ethics of embryonic stem cells—now and forever, cells without end. JAMA 284(24):3180–3184PubMedCrossRefGoogle Scholar
  13. 13.
    McLaren A (2000) Important differences between sources of embryonic stem cells. Nature 408(6812):513PubMedCrossRefGoogle Scholar
  14. 14.
    McLaren A (2001) Ethical and social considerations of stem cell research. Nature 414(6859):129–131PubMedCrossRefGoogle Scholar
  15. 15.
    Bradley JA, Bolton EM, Pedersen RA (2002) Stem cell medicine encounters the immune system. Nat Rev Immunol 2(11):859–871PubMedCrossRefGoogle Scholar
  16. 16.
    Drukker M, Katz G, Urbach A, Schuldiner M, Markel G, Itskovitz-Eldor J, Reubinoff B, Mandelboim O, Benvenisty N (2002) Characterization of the expression of MHC proteins in human embryonic stem cells. Proc Natl Acad Sci U S A 99(15):9864–9869PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Arnhold S, Klein H, Semkova I, Addicks K, Schraermeyer U (2004) Neurally selected embryonic stem cells induce tumor formation after long-term survival following engraftment into the subretinal space. Invest Ophthalmol Vis Sci 45(12):4251–4255PubMedCrossRefGoogle Scholar
  18. 18.
    Bieberich E, Silva J, Wang G, Krishnamurthy K, Condie BG (2004) Selective apoptosis of pluripotent mouse and human stem cells by novel ceramide analogues prevents teratoma formation and enriches for neural precursors in ES cell-derived neural transplants. J Cell Biol 167(4):723–734PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Wang Q, Matsumoto Y, Shindo T, Miyake K, Shindo A, Kawanishi M, Kawai N, Tamiya T, Nagao S (2006) Neural stem cells transplantation in cortex in a mouse model of Alzheimer’s disease. J Med Investig 53(1–2):61–69CrossRefGoogle Scholar
  20. 20.
    Jiang Y, Vaessen B, Lenvik T, Blackstad M, Reyes M, Verfaillie CM (2002) Multipotent progenitor cells can be isolated from postnatal murine bone marrow, muscle, and brain. Exp Hematol 30(8):896–904PubMedCrossRefGoogle Scholar
  21. 21.
    Banerjee S, Williamson DA, Habib N, Chataway J (2012) The potential benefit of stem cell therapy after stroke: an update. Vasc Health Risk Manag 8:569–580PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Alvarez-Dolado M, Pardal R, Garcia-Verdugo JM, Fike JR, Lee HO, Pfeffer K, Lois C, Morrison SJ, Alvarez-Buylla A (2003) Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature 425(6961):968–973PubMedCrossRefGoogle Scholar
  23. 23.
    Terada N, Hamazaki T, Oka M, Hoki M, Mastalerz DM, Nakano Y, Meyer EM, Morel L, Petersen BE, Scott EW (2002) Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 416(6880):542–545PubMedCrossRefGoogle Scholar
  24. 24.
    Do JT, Scholer HR (2005) Comparison of neurosphere cells with cumulus cells after fusion with embryonic stem cells: reprogramming potential. Reprod Fertil Dev 17(1–2):143–149PubMedCrossRefGoogle Scholar
  25. 25.
    Tada M, Takahama Y, Abe K, Nakatsuji N, Tada T (2001) Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Curr Biol 11(19):1553–1558PubMedCrossRefGoogle Scholar
  26. 26.
    Silva J, Chambers I, Pollard S, Smith A (2006) Nanog promotes transfer of pluripotency after cell fusion. Nature 441(7096):997–1001PubMedCrossRefGoogle Scholar
  27. 27.
    Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A (2003) Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 113(5):643–655PubMedCrossRefGoogle Scholar
  28. 28.
    Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M, Yamanaka S (2003) The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113(5):631–642PubMedCrossRefGoogle Scholar
  29. 29.
    Fan Y, Melhem MF, Chaillet JR (1999) Forced expression of the homeobox-containing gene Pem blocks differentiation of embryonic stem cells. Dev Biol 210(2):481–496PubMedCrossRefGoogle Scholar
  30. 30.
    Eiges R, Schuldiner M, Drukker M, Yanuka O, Itskovitz-Eldor J, Benvenisty N (2001) Establishment of human embryonic stem cell-transfected clones carrying a marker for undifferentiated cells. Curr Biol 11(7):514–518PubMedCrossRefGoogle Scholar
  31. 31.
    Niwa H, Miyazaki J, Smith AG (2000) Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet 24(4):372–376PubMedCrossRefGoogle Scholar
  32. 32.
    Bonab MM, Alimoghaddam K, Talebian F, Ghaffari SH, Ghavamzadeh A, Nikbin B (2006) Aging of mesenchymal stem cell in vitro. BMC Cell Biol 7:14PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Moussavi-Harami F, Duwayri Y, Martin JA, Moussavi-Harami F, Buckwalter JA (2004) Oxygen effects on senescence in chondrocytes and mesenchymal stem cells: consequences for tissue engineering. Iowa Orthop J 24:15–20PubMedPubMedCentralGoogle Scholar
  34. 34.
    Haleem-Smith H, Derfoul A, Okafor C, Tuli R, Olsen D, Hall DJ, Tuan RS (2005) Optimization of high-efficiency transfection of adult human mesenchymal stem cells in vitro. Mol Biotechnol 30(1):9–20PubMedCrossRefGoogle Scholar
  35. 35.
    Qu TY, Dong XJ, Sugaya I, Vaghani A, Pulido J, Sugaya K (2004) Bromodeoxyuridine increases multipotency of human bone marrow-derived stem cells. Restor Neurol Neurosci 22(6):459–468PubMedGoogle Scholar
  36. 36.
    Eisenberg LM, Eisenberg CA (2003) Stem cell plasticity, cell fusion, and transdifferentiation. Birth Defects Res C Embryo Today 69(3):209–218PubMedCrossRefGoogle Scholar
  37. 37.
    US 8906683 B2. Methods and materials for increasing potency of cellsGoogle Scholar
  38. 38.
    US 8058065 B2. Oct3/4, Klf4, c-Myc and Sox2 produce induced pluripotent stem cellsGoogle Scholar
  39. 39.
    Lowry WE, Richter L, Yachechko R, Pyle AD, Tchieu J, Sridharan R, Clark AT, Plath K (2008) Generation of human induced pluripotent stem cells from dermal fibroblasts. Proc Natl Acad Sci U S A 105(8):2883–2888PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Park IH, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, Lerou PH, Lensch MW, Daley GQ (2008) Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451(7175):141–146PubMedCrossRefGoogle Scholar
  41. 41.
    Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318(5858):1917–1920PubMedCrossRefGoogle Scholar
  42. 42.
    Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676CrossRefGoogle Scholar
  43. 43.
    Zhang XY, La Russa VF, Reiser J (2004) Transduction of bone-marrow-derived mesenchymal stem cells by using lentivirus vectors pseudotyped with modified RD114 envelope glycoproteins. J Virol 78(3):1219–1229PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Kuroda T, Tada M, Kubota H, Kimura H, Hatano SY, Suemori H, Nakatsuji N, Tada T (2005) Octamer and Sox elements are required for transcriptional cis regulation of Nanog gene expression. Mol Cell Biol 25(6):2475–2485PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Rodda DJ, Chew JL, Lim LH, Loh YH, Wang B, Ng HH, Robson P (2005) Transcriptional regulation of nanog by OCT4 and SOX2. J Biol Chem 280(26):24731–24737PubMedCrossRefGoogle Scholar
  46. 46.
    Okita K, Ichisaka T, Yamanaka S (2007) Generation of germline-competent induced pluripotent stem cells. Nature 448(7151):313–317PubMedCrossRefGoogle Scholar
  47. 47.
    Awaya A, Kobayashi H, Horikomi K, Tanaka S, Kabir AM, Yokoyama K, Ohno H, Kato K, Kitahara T, Tomino I et al (1993) Neurotropic pyrimidine heterocyclic compounds. I. The newly synthesized pyrimidine compounds promote neurite outgrowth of GOTO and neuro 2a neuroblastoma cell lines, and potentiate nerve growth factor (NGF)- induced neurite sprouting of PC 12 cells. Biol Pharm Bull 16:248–253PubMedCrossRefGoogle Scholar
  48. 48.
    Koyama Y, Awaya A, Ishikawa N, Fujita S, Tomino I, Yokoyama K, Araki S, Takesue M, Kato K, Ishiguro M, Kitahara T, Kihara N, Baba A (1997) Neurotropic pyrimidine heterocyclic compounds. II. Effects of novel neurotropic pyrimidine derivatives on astrocytic morphological differentiation. Biol Pharm Bull 20:138–141PubMedCrossRefGoogle Scholar
  49. 49.
    Ohbayashi K, Inoue HK, Awaya A, Kobayashi S, Kohga H, Nakamura M, Ohye C (1996) Peripheral nerve regeneration in a silicone tube: effect of collagen sponge prosthesis, laminin, and pyrimidine compound administration. Neurol Med Chir (Tokyo) 36:428–433CrossRefGoogle Scholar
  50. 50.
    Sanjo N, Owada K, Kobayashi T, Mizusawa H, Awaya A, Michikawa M (1998) A novel neurotrophic pyrimidine compound MS-818 enhances neurotrophic effects of basic fibroblast growth factor. J Neurosci Res 54:604–612PubMedCrossRefGoogle Scholar
  51. 51.
    Jiang XM, Ohnishi A, Yamamoto T, Murai Y, Awaya A, Ikeda M (1995) The effect of MS-818, a pyrimidine compound, on the regeneration of peripheral-nerve fibers of mice after a crush injury. Acta Neuropathol 90:130–134PubMedCrossRefGoogle Scholar
  52. 52.
    Yasuhara S, Kashiwagi S, Ito H, Awaya A (1995) The neurotrophic pyrimidine heterocyclic compound MS-818 promotes the angiogenesis induced by basic FGF. Int J Clin Pharmacol Res 15:167–174PubMedGoogle Scholar
  53. 53.
    Watanabe S, Wang XE, Hirose M, Osada T, Yoshizawa T, Tanaka H, Itatsu T, Nakajima M, Yamamoto J, Miwa H, Miyazaki A, Awaya A, Sato N (1998) A neurotrophic pyrimidine compound, MS-818, enhances EGF-induced restoration of gastric epithelial wounds in vitro. J Clin Gastroenterol 27(Suppl 1):S105–S109PubMedCrossRefGoogle Scholar
  54. 54.
    Sugiyama N, Yoshimura A, Fujitsuka C, Iwata H, Awaya A, Mori S, Yoshizato H, Fujitsuka N (2002) Acceleration by MS-818 of early muscle regeneration and enhanced muscle recovery after surgical transection. Muscle Nerve 25:218–229PubMedCrossRefGoogle Scholar
  55. 55.
    Shimoda N, Mutou Y, Shimura N, Tsukimoto M, Awaya A, Kojima S (2010) Effect of heterocyclic pyrimidine compounds on UVB-induced cell damage in human keratinocytes and on melanogenesis in mouse B16 cells. Biol Pharm Bull 33:862–868PubMedCrossRefGoogle Scholar
  56. 56.
    Sugaya K, Merchant S (2011) Composition for treating or delaying the onset of hair loss. In: USPTO (ed), USAGoogle Scholar
  57. 57.
    Sugaya K, Qu T (2013) Use of modified pyrimidine compounds to promote stem cell migration and proliferation. In: USPTO (ed), USAGoogle Scholar
  58. 58.
    Sugaya K, Merchant S (2008) How to approach Alzheimer’s disease therapy using stem cell technologies. J Alzheimers Dis 15:241–254PubMedCrossRefGoogle Scholar
  59. 59.
    Blurton-Jones M, Kitazawa M, Martinez-Coria H, Castello NA, Muller FJ, Loring JF, Yamasaki TR, Poon WW, Green KN, LaFerla FM (2009) Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc Natl Acad Sci U S A 106:13594–13599PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Kim J-H, Auerbach JM, Rodrıguez-Gomez JA, Velasco I, Gavin D, Lumelsky N, Lee S-H, Nguyen J, Sanchez-Pernaute R, Bankiewicz K, McKay R (2002) Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease. Nature 418:50–56PubMedCrossRefGoogle Scholar
  61. 61.
    McBride JL, Behrstock SP, Chen EY, Jakel RJ, Siegel I, Svendsen CN, Kordower JH (2004) Human neural stem cell transplants improve motor function in a rat model of Huntington’s disease. J Comp Neurol 475:211–219PubMedCrossRefGoogle Scholar
  62. 62.
    Ryu JK, Kim J, Cho SJ, Hatori K, Nagai A, Choi HB, Lee MC, McLarnon JG, Kim SU (2004) Proactive transplantation of human neural stem cells prevents degeneration of striatal neurons in a rat model of Huntington disease. Neurobiol Dis 16:68–77PubMedCrossRefGoogle Scholar
  63. 63.
    Yasuhara T, Matsukawa N, Hara K, Yu G, Xu L, Maki M, Kim SU, Borlongan CV (2006) Transplantation of human neural stem cells exerts neuroprotection in a rat model of Parkinson’s disease. J Neurosci 26:12497–12511PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Diamond A, Jankovic J (2006) Treatment of advanced Parkinson’s disease. Expert Rev Neurother 6:1181–1197PubMedCrossRefGoogle Scholar
  65. 65.
    Lindenbach D, Bishop C (2013) Critical involvement of the motor cortex in the pathophysiology and treatment of Parkinson’s disease. Neurosci Biobehav Rev 37:2737–2750PubMedCrossRefGoogle Scholar
  66. 66.
    Oh MY, Abosch A, Kim SH, Lang AE, Lozano AM (2002) Long-term hardware- related complications of deep brain stimulation. Neurosurgery 50:1268–1274. discussion 1274–1266PubMedGoogle Scholar
  67. 67.
    Lie DC, Dziewczapolski G, Willhoite AR, Kaspar BK, Shults CW, Gage FH (2002) The adult substantia nigra contains progenitor cells with neurogenic potential. J Neurosci 22:6639–6649PubMedCrossRefGoogle Scholar
  68. 68.
    Hoglinger GU, Rizk P, Muriel MP, Duyckaerts C, Oertel WH, Caille I, Hirsch EC (2004) Dopamine depletion impairs precursor cell proliferation in Parkinson disease. Nat Neurosci 7:726–735PubMedCrossRefGoogle Scholar
  69. 69.
    Boulet S, Mounayar S, Poupard A, Bertrand A, Jan C, Pessiglione M, Hirsch EC, Feuerstein C, Francois C, Feger J, Savasta M, Tremblay L (2008) Behavioral recovery in MPTP-treated monkeys: neurochemical mechanisms studied by intrastriatal microdialysis. J Neurosci 28:9575–9584PubMedCrossRefGoogle Scholar
  70. 70.
    Mounayar S, Boulet S, Tande D, Jan C, Pessiglione M, Hirsch EC, Feger J, Savasta M, Francois C, Tremblay L (2007) A new model to study compensatory mechanisms in MPTP-treated monkeys exhibiting recovery. Brain 130:2898–2914PubMedCrossRefGoogle Scholar
  71. 71.
    Ogawa N, Mizukawa K, Hirose Y, Kajita S, Ohara S, Watanabe Y (1987) MPTP- induced parkinsonian model in mice: biochemistry, pharmacology and behavior. Eur Neurol 26(Suppl 1):16–23PubMedCrossRefGoogle Scholar
  72. 72.
    Brown JP, Couillard-Despres S, Cooper-Kuhn CM, Winkler J, Aigner L, Kuhn HG (2003) Transient expression of doublecortin during adult neurogenesis. J Comp Neurol 467:1–10PubMedCrossRefGoogle Scholar
  73. 73.
    Jankovic J (2002) Levodopa strengths and weaknesses. Neurology 58:S19–S32PubMedCrossRefGoogle Scholar
  74. 74.
    LeWitt PA (2008) Levodopa for the treatment of Parkinson’s disease. N Engl J Med 359:2468–2476PubMedCrossRefGoogle Scholar
  75. 75.
    Mitsuyama T, Kawamata T, Yamane F, Awaya A, Hori T (2002) Role of a synthetic pyrimidine compound, MS-818, in reduction of infarct size and amelioration of sensorimotor dysfunction following permanent focal cerebral ischemia in rats. J Neurosurg 96:1072–1076PubMedCrossRefGoogle Scholar
  76. 76.
    Wenk GL (2003) Neuropathologic changes in Alzheimer’s disease. J Clin Psychiatry 64(Suppl 9):7–10PubMedGoogle Scholar
  77. 77.
    Cheng SV, Nadeau JH, Tanzi RE, Watkins PC, Jagadesh J, Taylor BA, Haines JL, Sacchi N, Gusella JF (1988) Comparative mapping of DNA markers from the familial Alzheimer disease and Down syndrome regions of human chromosome 21 to mouse chromosomes 16 and 17. Proc Natl Acad Sci U S A 85:6032–6036PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Levy-Lahad E, Wijsman EM, Nemens E, Anderson L, Goddard KA, Weber JL, Bird TD, Schellenberg GD (1995) A familial Alzheimer’s disease locus on chromosome 1. Science 269:970–973PubMedCrossRefGoogle Scholar
  79. 79.
    Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K et al (1995) Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s disease. Nature 375:754–760PubMedCrossRefGoogle Scholar
  80. 80.
    Selkoe DJ (2001) Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev 81:741–766PubMedCrossRefGoogle Scholar
  81. 81.
    Kitaguchi N, Takahashi Y, Tokushima Y, Shiojiri S, Ito H (1988) Novel precursor of Alzheimer’s disease amyloid protein shows protease inhibitory activity. Nature 331:530–532PubMedCrossRefGoogle Scholar
  82. 82.
    Sandbrink R, Masters CL, Beyreuther K (1994) Beta A4-amyloid protein precursor mRNA isoforms without exon 15 are ubiquitously expressed in rat tissues including brain, but not in neurons. J Biol Chem 269:1510–1517PubMedGoogle Scholar
  83. 83.
    Sisodia SS, Koo EH, Hoffman PN, Perry G, Price DL (1993) Identification and transport of full-length amyloid precursor proteins in rat peripheral nervous system. J Neurosci 13:3136–3142PubMedCrossRefGoogle Scholar
  84. 84.
    Sprecher CA, Grant FJ, Grimm G, O’Hara PJ, Norris F, Norris K, Foster DC (1993) Molecular cloning of the cDNA for a human amyloid precursor protein homolog: evidence for a multigene family. Biochemistry 32:4481–4486PubMedCrossRefGoogle Scholar
  85. 85.
    Wasco W, Bupp K, Magendantz M, Gusella JF, Tanzi RE, Solomon F (1992) Identification of a mouse brain cDNA that encodes a protein related to the Alzheimer disease-associated amyloid beta protein precursor. Proc Natl Acad Sci U S A 89:10758–10762PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Wasco W, Gurubhagavatula S, Paradis MD, Romano DM, Sisodia SS, Hyman BT, Neve RL, Tanzi RE (1993) Isolation and characterization of APLP2 encoding a homologue of the Alzheimer’s associated amyloid beta protein precursor. Nat Genet 5:95–100PubMedCrossRefGoogle Scholar
  87. 87.
    Daigle I, Li C (1993) apl-1, a Caenorhabditis elegans gene encoding a protein related to the human beta-amyloid protein precursor. Proc Natl Acad Sci U S A 90:12045–12049PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Luo L, Tully T, White K (1992) Human amyloid precursor protein ameliorates behavioral deficit of flies deleted for Appl gene. Neuron 9:595–605PubMedCrossRefGoogle Scholar
  89. 89.
    Lammich S, Kojro E, Postina R, Gilbert S, Pfeiffer R, Jasionowski M, Haass C, Fahrenholz F (1999) Constitutive and regulated alpha-secretase cleavage of Alzheimer’s amyloid precursor protein by a disintegrin metalloprotease. Proc Natl Acad Sci U S A 96:3922–3927PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Sinha S, Anderson JP, Barbour R, Basi GS, Caccavello R, Davis D, Doan M, Dovey HF, Frigon N, Hong J, Jacobson-Croak K, Jewett N, Keim P, Knops J, Lieberburg I, Power M, Tan H, Tatsuno G, Tung J, Schenk D, Seubert P, Suomensaari SM, Wang S, Walker D, Zhao J, McConlogue L, John V (1999) Purification and cloning of amyloid precursor protein beta-secretase from human brain. Nature 402:537–540PubMedCrossRefGoogle Scholar
  91. 91.
    Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, Teplow DB, Ross S, Amarante P, Loeloff R, Luo Y, Fisher S, Fuller J, Edenson S, Lile J, Jarosinski MA, Biere AL, Curran E, Burgess T, Louis JC, Collins F, Treanor J, Rogers G, Citron M (1999) Beta-secretase cleavage of Alzheimer’s amyloid precursor 136protein by the transmembrane aspartic protease BACE. Science 286:735–741PubMedCrossRefGoogle Scholar
  92. 92.
    Yan R, Bienkowski MJ, Shuck ME, Miao H, Tory MC, Pauley AM, Brashier JR, Stratman NC, Mathews WR, Buhl AE, Carter DB, Tomasselli AG, Parodi LA, Heinrikson RL, Gurney ME (1999) Membrane-anchored aspartyl protease with Alzheimer’s disease beta-secretase activity. Nature 402:533–537PubMedCrossRefGoogle Scholar
  93. 93.
    Edbauer D, Winkler E, Regula JT, Pesold B, Steiner H, Haass C (2003) Reconstitution of gamma-secretase activity. Nat Cell Biol 5:486–488PubMedCrossRefGoogle Scholar
  94. 94.
    Leissring MA, Murphy MP, Mead TR, Akbari Y, Sugarman MC, Jannatipour M, Anliker B, Muller U, Saftig P, De Strooper B, Wolfe MS, Golde TE, LaFerla FM (2002) A physiologic signaling role for the gamma -secretase-derived intracellular fragment of APP. Proc Natl Acad Sci U S A 99:4697–4702PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Kim HS, Kim EM, Lee JP, Park CH, Kim S, Seo JH, Chang KA, Yu E, Jeong SJ, Chong YH, Suh YH (2003) C-terminal fragments of amyloid precursor protein exert neurotoxicity by inducing glycogen synthase kinase-3beta expression. FASEB J 17:1951–1953PubMedCrossRefGoogle Scholar
  96. 96.
    Cao X, Sudhof TC (2001) A transcriptionally [correction of transcriptively] active complex of APP with Fe65 and histone acetyltransferase Tip60. Science 293:115–120PubMedCrossRefGoogle Scholar
  97. 97.
    Rossjohn J, Cappai R, Feil SC, Henry A, McKinstry WJ, Galatis D, Hesse L, Multhaup G, Beyreuther K, Masters CL, Parker MW (1999) Crystal structure of the N137 terminal, growth factor-like domain of Alzheimer amyloid precursor protein. Nat Struct Biol 6:327–331PubMedCrossRefGoogle Scholar
  98. 98.
    Small DH, Clarris HL, Williamson TG, Reed G, Key B, Mok SS, Beyreuther K, Masters CL, Nurcombe V (1999) Neurite-outgrowth regulating functions of the amyloid protein precursor of Alzheimer’s disease. J Alzheimers Dis 1:275–285PubMedCrossRefGoogle Scholar
  99. 99.
    Ninomiya H, Roch JM, Sundsmo MP, Otero DA, Saitoh T (1993) Amino acid sequence RERMS represents the active domain of amyloid beta/A4 protein precursor that promotes fibroblast growth. J Cell Biol 121:879–886PubMedCrossRefGoogle Scholar
  100. 100.
    Small DH, Nurcombe V, Reed G, Clarris H, Moir R, Beyreuther K, Masters CL (1994) A heparin-binding domain in the amyloid protein precursor of Alzheimer’s disease is involved in the regulation of neurite outgrowth. J Neurosci 14:2117–2127PubMedCrossRefGoogle Scholar
  101. 101.
    Nishimoto I, Okamoto T, Matsuura Y, Takahashi S, Okamoto T, Murayama Y, Ogata E (1993) Alzheimer amyloid protein precursor complexes with brain GTP-binding protein G(o). Nature 362:75–79PubMedCrossRefGoogle Scholar
  102. 102.
    De Strooper B, Annaert W (2000) Proteolytic processing and cell biological functions of the amyloid precursor protein. J Cell Sci 113(Pt 11):1857–1870PubMedGoogle Scholar
  103. 103.
    Mondal D, Pradhan L, LaRussa VF (2004) Signal transduction pathways involved in the lineage-differentiation of NSCs: can the knowledge gained from blood be used in the brain? Cancer Investig 22:925–943CrossRefGoogle Scholar
  104. 104.
    Thoma B, Bird TA, Friend DJ, Gearing DP, Dower SK (1994) Oncostatin M and leukemia inhibitory factor trigger overlapping and different signals through partially shared receptor complexes. J Biol Chem 269:6215–6222PubMedGoogle Scholar
  105. 105.
    Wijdenes J, Heinrich PC, Muller-Newen G, Roche C, Gu ZJ, Clement C, Klein B (1995) Interleukin-6 signal transducer gp130 has specific binding sites for different cytokines as determined by antagonistic and agonistic anti-gp130 monoclonal antibodies. Eur J Immunol 25:3474–3481PubMedCrossRefGoogle Scholar
  106. 106.
    Wang Y, Fuller GM (1994) Phosphorylation and internalization of gp130 occur after IL-6 activation of Jak2 kinase in hepatocytes. Mol Biol Cell 5:819–828PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    He F, Ge W, Martinowich K, Becker-Catania S, Coskun V, Zhu W, Wu H, Castro D, Guillemot F, Fan G, de Vellis J, Sun YE (2005) A positive autoregulatory loop of Jak- STAT signaling controls the onset of astrogliogenesis. Nat Neurosci 8:616–625PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Bonni A, Sun Y, Nadal-Vicens M, Bhatt A, Frank DA, Rozovsky I, Stahl N, Yancopoulos GD, Greenberg ME (1997) Regulation of gliogenesis in the central nervous system by the JAK-STAT signaling pathway. Science 278:477–483PubMedCrossRefGoogle Scholar
  109. 109.
    Kageyama R, Ohtsuka T, Hatakeyama J, Ohsawa R (2005) Roles of bHLH genes in neural stem cell differentiation. Exp Cell Res 306:343–348PubMedCrossRefGoogle Scholar
  110. 110.
    Fassa A, Mehta P, Efthimiopoulos S (2005) Notch 1 interacts with the amyloid precursor protein in a Numb-independent manner. J Neurosci Res 82:214–224PubMedCrossRefGoogle Scholar
  111. 111.
    Oh SY, Ellenstein A, Chen CD, Hinman JD, Berg EA, Costello CE, Yamin R, Neve RL, Abraham CR (2005) Amyloid precursor protein interacts with notch receptors. J Neurosci Res 82:32–42PubMedCrossRefGoogle Scholar
  112. 112.
    Kamakura S, Oishi K, Yoshimatsu T, Nakafuku M, Masuyama N, Gotoh Y (2004) Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT signalling. Nat Cell Biol 6:547–554PubMedCrossRefGoogle Scholar
  113. 113.
    Kwak YD, Brannen CL, Qu T, Kim HM, Dong X, Soba P, Majumdar A, Kaplan A, Beyreuther K, Sugaya K (2006a) Amyloid precursor protein regulates differentiation of human neural stem cells. Stem Cells Dev 15(3):381–389PubMedCrossRefGoogle Scholar
  114. 114.
    Kwak YD, Choumkina E, Sugaya K (2006b) Amyloid precursor protein is involved in staurosporine induced glial differentiation of neural progenitor cells. Biochem Biophys Res Commun 344(1):431–437PubMedCrossRefGoogle Scholar
  115. 115.
    Marutle A, Ohmitsu M, Nilbratt M, Greig NH, Nordberg A, Sugaya K (2007) Modulation of human neural stem cell differentiation in Alzheimer (APP23) transgenic mice by phenserine. Proc Natl Acad Sci U S A 104(30):12506–12511PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Burnett School of Biomedical Sciences, College of Medicine, University of Central FloridaOrlandoUSA

Personalised recommendations

Cite chapter

Buy options