Colostral proline-rich polypeptides -immunoregulatory properties and prospects of therapeutic use in alzheimer's disease

Current Alzheimer Research

Volumn 7, Issue 4, 2010, Pages 323-333

  Janusz, M ^a   Zabllocka A ^a  

^a INSTITUTE OF IMMUNOLOGY AND EXPERIMENTAL THERAPY   (Poland)

Author keywords

Alzheimer's disease; Cellular oxidative metabolism; Cytokine induction; Immunomodulation; Proline rich polypeptide complex prp colostrinin clnspi_suptmspii_sup

Indexed keywords

4 HYDROXYNONENAL; ALZHEIMER DISEASE VACCINE; AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN ANTIBODY; AMYLOID BETA PROTEIN[1-42]; ARIZEPT; CHOLINESTERASE INHIBITOR; COLOSTRININ; COPPER; DNA VACCINE; DONEPEZIL; GALANTAMINE; GINKGO BILOBA EXTRACT; INTERFERON; INTERLEUKIN 10; INTERLEUKIN 1BETA; INTERLEUKIN 6; NONSTEROID ANTIINFLAMMATORY AGENT; PENTAPEPTIDE; PLACEBO; PROLINE RICH PROTEIN; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN METABOLITE; RETINOIC ACID; RIVASTIGMINE; ROFECOXIB; SALVIA MILTIORRHIZA EXTRACT; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALPROIC ACID; ZINC;

ALZHEIMER DISEASE; ANXIETY; ARTICLE; ASEPTIC MENINGITIS; ASEPTIC MENINGOENCEPHALITIS; BRAIN PROTECTION; CELL ACTIVATION; CELL DIFFERENTIATION; CELL MATURATION; CELL PROLIFERATION; CELLULAR IMMUNITY; CLINICAL TRIAL; COGNITION; COLOSTRUM; CYTOKINE PRODUCTION; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; HUMAN; HUMORAL IMMUNITY; HYDROPHOBICITY; IMMUNOREGULATION; INSOMNIA; LEARNING; LOGORRHEA; MOLECULAR WEIGHT; NERVE FIBER GROWTH; NONHUMAN; OXIDATION REDUCTION REACTION; PRIORITY JOURNAL; PROTEIN AGGREGATION; SIDE EFFECT; THYMOCYTE;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; CLINICAL TRIALS AS TOPIC; HUMANS; NOOTROPIC AGENTS; OXIDATIVE STRESS; PEPTIDES;

EID: 77954024099     PISSN: 15672050     EISSN: None     Source Type: Journal    
DOI: 10.2174/156720510791162377     Document Type: Article

References (149)

1. Meduri R, Campos E, Scorolli L, De Vinci C, Pizza G, Viza D. Efficacy of transfer factor in treating patients with recurrent ocular herpes infections. Biotherapy 9: 61-6 (1996).
2. Pizza G, Viza D, De Vinci C, Palareti A, Cuzzocrea D, Fornarola V, et al. Orally administered HSV-specific transfer factor (TF) prevents genitial or labial herpes relapses. Biotherapy 9: 67-72 (1996).
3. Orzechowska B, Janusz M, Domaraczenko B, Bach-Olszewska Z. Antiviral effect of proline-rich polypeptide in murine resident peritoneal cells. Acta Virol 42: 75-8 (1998).
4. Prased U, bin Jalaludin MA, Rajadurai P, Pizza G, De Vinci C, Viza D, et al. Transfer factor with anti-EBV activity as an adjuvant therapy for nasopharyngeal carcinoma: a pilot study. Biotherapy 9: 109-15 (1996).
5. Ferrer-Argote VE, Romero-Cabello R, Hern,ez-Mendoza L. Successful treatment of severe complicated measles with non-specific transfer factor. In Vivo 8: 555-7 (1994).
6. Raise E, Guerra L, Viza D, Pizza G, De Vinci C, Schiattone ML, et al. Preliminary results in HIV-infected patients treated with transfer factor (TF) and zidovudine (ZDV). Biotherapy 9: 49-54 (1996).
7. Otvos L. Antibacterial peptides isolated from insects. J Pept Sci 6: 497-511 (2000).
8. Otvos L. The short proline-rich antibacterial peptide family. Cell Mol Life Sci 59: 1138-50 (2002).
9. Li WF, Ma GX, Zhou XX. Apidaecin-type peptides: biodiversity, structure function relationships and mode of action. Peptides 27: 2350-9 (2006).
10. Huberman L, Gollop N, Mumcuoglu KY, Breuer E, Bhusare SR, Shai Y, et al. Antibacterial substances of low molecular weight isolated from the blowfly, Lucilia sericata. Med Vet Entomol 21: 127-31 (2007).
11. Altincicek B, Vilcinskas A. Septic injury-inducible genes in medicinal maggots of the green blow fly Lucilia sericata. Insect Mol Biol 18: 119-25 (2009).
12. Yannick G, Romestand B, Fievet J, Schmidt P, Destoumieux-Garzon D,Vandenbulcke F, et al. Oyster hemocytes express a proline-rich peptide displaying synergistic antimicrobial activity with a defensin. Mol Immunol 46: 516-22 (2009).
13. Park MH, Park SY, Kim Y. Induction of proline-rich tyrosine kinase2 (Pyk2) through C/EBPbeta is involved in PMA-induced monocyte differentiation. FEBS Lett 582: 415-22 (2008).
14. Gutenberg A, Brück W, Buchfelder M, Ludwig HC. Expression of tyrosine kinases FAK and Pyk2 in 331 human astrocytomas. Acta Neuropathol (Ber) 108: 224-30 (2004).
15. Lipinski CA, Tran NL, Menashi E, Rohl C, Kloss J, Bay RC, et al. The tyrosine kinase pyk2 promote migration and invasion of glioma cells. Neoplasia 7: 435-45 (2005).
16. Stanzione R, Picascia A, Chieffi P, Imbimbo C, Palmieri A, Mirone A, et al. Variations of proline-rich kinase Pyk2 expression correlate with prostate cancer progression. Lab Invest 81: 51-9 (2001).
17. Knight GL, Grainger JR, Gallimore PH, Roberts S. Cooperation between different forms of the human papillomavirus type E4 protein to block cell cycle progression and cellular DNA synthesis. J Virol 78: 13920-33 (2004).
18. Golubovskaya VM, Finch R, Zheng M, Kurenova EV, Cance WG. The 7-aminoacid site in the proline-rich region of the N-terminal domain of p53 is involved in the interaction with FAK and is critical for p53 functioning. Biochem J 411: 151-60 (2008).
19. Manavathi B, Nair RA, Wang RA, Kumar R, Vadlamudi RK. Proline-, glutamic acid-, and leucine-rich proline-1 is essential in growth factor regulation of signal transducers and activators of transcription 3 activation. Cancer Res 65: 571-7 (2005).
20. Silva CA, Portaro FC, Fernandes BL, Ianzer DA, Guerriero JR, Gomez CL, et al. Tissue distribution in mice of BPP 10c, a potent proline-rich anti-hypertensive peptide of Bothropus jararaca. Toxicon 51: 515-23 (2008).
21. Li H, Schopfer LM, Masson P, Lockridge O. Lamellipodin prolinerich peptides associated with native plasma butyrylocholesterase tetramers. Biochem J 411: 425-32 (2008).
22. Abrahamyan SS, Sarkissian JS, Meliksetyan IB, Galoyan AA. Survival of trauma-injured neurons in rats brain by treatment with proline-rich polypeptide (PRP-1): an immunohistochemical study. Neurochem Res 29: 695-708 (2004).
23. Davtyan TK, Manukyan HA, Mkrtchyan NR, Avetisyan SA, Galoyan AA. Hypothalamic proline-rich polypeptide is a regulator of oxidative burst in human neutrophils and monocytes. Neuroimmunomodulation 12: 70-84 (2005).
24. Davtyan TK, Manukyan HA, Hakopyan GS, Mkrtchyan R, Avetisyan SA, Galoyan AA. Hypothalamic proline-rich polypeptide is an oxidative burst regulator. Neurochem Res 30: 297-309 (2005).
25. Galoyan AA, Korochkin LI, Rybalkina EJ, Pavloa GV, Saburina IN, Zaralski EI, et al. Hypothalamic proline-rich polypeptide enhances bone marrow colony-forming cell proliferation and stromal progenitor cell differentiation. Cell Transplant 17: 1061-6 (2008).
26. Kim JE, Ryu I, Kim WJ, Song OK, Ryu J, Kwon MY, et al. Proline-rich transcript in brain protein induces stress granule for mation. Mol Cell Biol 28: 803-13 (2008).
27. Pascal C, Bigey F, Ratomahenine R, Boze H, Moulin G, Sarni-Manchado P. Overexpression and characterization of two human salivary proline-rich proteins. Protein Exp Purif 47: 524-32 (2006).
28. Proctor GB, Pramanik R, Carpenter GH, Rees GD. Salivary proteins interact with dietary constituents to modulate tooth staining. J Dent Res 84: 73-8 (2005).
29. Walz A, Stühler K, Wattenberg A, Hawranke E, Meyer HE, Schmaltz G. Proteome analysis of glandular parotid and subman-dibular-sublingual saliva in composition to whole human saliva by two-dimensional gel electrophoresis. Proteomics 6: 1631-9 (2006).
30. Zakhary GM, Clark RM, Bidichandani SI, Owen WL, Slayton RL, Levin M. Acidic proline-rich protein Db and caries in young children. J Dent Res 86: 1176-80 (2007).
31. Cai K, Hagerman AE, Minto RE, Bennick A. Decreased polyphenol transport across cultured intestinal cells by a salivary prolinerich protein. Biochem Pharmacol 28: 1570-80 (2006).
32. Sarni-Manchado P, Canals-Bosch JM, Mazerolles G, Cheynier V. Influence of the glycosylation of human salivary proteins on their interactions with condensed tannins. J Agric Food Chem 56: 9563-9 (2008).
33. Robinovitch MR, Ashley RL, Iversen JM, Vigoren EM, Oppen-heim FG, Lamkin M. Parotid salivary basic proline-rich proteins inhibit HIV infectivity. Oral Dis 7: 89-93 (2001).
34. Fung KY, Morris C, Sathe S, Vigoren EM, Oppenheim FG, Lam-kin M. Characterization of the in vivo forms of lacrimal-specific proline-rich proteins in human tear fluid. Proteomics 4: 3953-9 (2004).
35. Lisowski J, Janusz M, Tyran B, Morawiecki AG, Bia kowska GH. Immunoglobulins of colostrum -III: comparative studies of ovine serum and colostral IgG1 and IgG2. Immunochemistry 12: 159-66 (1975).
36. Janusz M, Lisowski J, Franek F. Isolation and characterization of a proline-rich polypeptide from ovine colostrum. FEBS Lett 49: 276-9 (1974).
37. Janusz M, Starocik K, Zimecki M, Wieczorek Z, Lisowski J. Chemical and physical characterization of a proline-rich polypep-tide from sheep colostrum. Biochem J 199: 9-15 (1981).
38. Kruzel ML, Janusz M, Lisowski J, Fischleigh RV, Georgiades JA. Towards an understanding of biological role of Colostrinin pep-tides. J Mol Neurosci 17: 379-8 (2001).
39. Piasecki E, Inglot AD, Winiarska M, Krukowska K, Janusz M, Lisowski J. Coincidence between spontaneous release of interferon and tumor necrosis factor by colostral leukocytes and the produc-tion of a colostrinine by human mammary gland after normal deliv-ery. Arch Immunol Ther Exp 45: 109-17 (1997).
40. Sokołowska A, Bednarz R, Pacewicz M, Georgiades JA, Wilusz T, Polanowski A. Colostrum from different mammalian species -A rich source of colostrinin. Int Dairy J 18: 204-9 (2008).
41. Wieczorek Z, Zimecki M, Janusz M, Starościk K, Lisowski J. Proline-rich polypeptide from ovine colostrum: its effect on skin permeability and on the immune response. Immunology 36: 875-81 (1979).
42. Lisowski J, Wieczorek Z, Janusz M, Zimecki M. Proline-rich poly-peptide (PRP) from ovine colostrum. Bi-directional modulation of binding of peanut aggutinin, resistance to hydrocortisone, and helper activity in murine thymocytes. Arch Immunol Ther Exp 36: 381-93 (1988).
43. Zimecki M, Lisowski J, Hraba T, Wieczorek Z, Janusz M, Starocik K. The effect of a proline-rich polypeptide (PRP) on hu-moral immune response. I. Distinct effect of PRP on the cell prop-erties of mouse glass-nonadherent (NAT) and glass-adherent (GAT) thymocytes in thymectomized mice. Arch Immunol Ther Exp 32: 191-6 (1984).
44. Zimecki M, Lisowski J, Hraba T, Wieczorek Z, Janusz M, Staro cik K. The effect of a proline-rich polypeptide on the hu-moral immune response. II. PRP induces differentiation of helper cells from glass-nonadherent (NAT) and suppressor cells from glass-adherent (GAT) thymocytes. Arch Immunol Ther Exp 32: 197-201 (1984).
45. Zimecki M, Staro cik K, Janusz M, Lisowski J, Wieczorek Z. The inhibitory activity of a proline-rich polypeptide (PRP) on the im-mune response to polyvinylpyrrolidone (PVP). Arch Immunol Ther Exp 31: 681-9 (1983).
46. Zimecki M, Janusz M, Staro cik K, Lisowski J, Wieczorek Z. Effect of a proline-rich polypeptide on donor cells in graft-versus-host reaction. Immunology 47: 141-7 (1982).
47. Wieczorek Z, Zimecki M, Janusz M, Lisowski J, Staro cik K. Cells involved in autologous rosette formation in mice. I. Two different subpopulation of thymocytes regulating autologous rosette forma-tion. Arch Immunol Ther Exp 32: 537-41 (1984).
48. Sokal I, Janusz M, Miecznikowska H, Kupryszewski G, Lisowski J. Effect of Colostrinin, an immunomodulatory proline-rich poly-peptide from ovine colostrum, on sialidase and -galactosidase ac-tivities in murine thymocytes. Arch Immunol Ther Exp 46: 193-8 (1998).
49. Zimecki M, Pierce CW, Janusz M, Wieczorek Z, Lisowski J. Pro-liferative response of T lymphocytes to a proline-rich polypeptide (PRP): PRP mimics mitogenic activity of IL-1. Arch Immunol Ther Exp 35: 339-49 (1987).
50. Wieczorek Z, Zimecki M, Spiegel K, Lisowski J, Janusz M. Differ-entiation of T cells into helper cells from immature precursors: identification of a target cell for a proline-rich polypeptide (PRP). Arch Immunol Ther Exp 37: 313-22 (1989).
51. Janusz M, Staro cik K, Zimecki M, Wieczorek Z, Lisowski J. A proline-rich polypeptide (PRP) with immunoregulatory properties isolated from ovine colostrum. Murine thymocytes have on their surface a receptor specific for PRP. Arch Immunol Ther Exp 34: 427-36 (1986).
52. Julius M, Janusz M, Lisowski J. A colostral protein that induces the growth and differentiation of resting B lymphocytes. J Immunol 140: 1366-71 (1988).
53. Zimecki M, Hraba T, Janusz M, Lisowski J, Wieczorek Z. Effect of a proline-rich polypeptide (PRP) on the development of hemolytic anemia and survival of New Zealand Black (NZB) mice. Arch Im-munol Ther Exp 39: 461-7 (1991).
54. Zabłocka A, Janusz M, Macała J, Lisowski J. A proline-rich poly-peptide complex and its nonapeptide fragment inhibit nitric oxide production induced in mice. Regul Pept 125: 35-9 (2005).
55. Staro cik K, Janusz M, Zimecki M, Wieczorek Z, Lisowski J. Immunologically active nonapeptide fragment of a proline-rich polypeptide from ovine colostrum: amino acid sequence and im-munoregulatory properties. Mol Immunol 20: 1277-82 (1983).
56. Janusz M, Błaszczyk B. Effect of a proline-rich polypeptide on IgG level. Arch Immunol Ther Exp 44: 23-6 (1996).
57. Zabłocka A, Janusz M, Rybka K, Wirkus-Romanowska I, Kupryszewski G, Lisowski J. Cytokine-inducing activity of a proline-ich polypeptide complex (PRP) from ovine colostrum and its active nonapeptide fragment analogs. Eur Cytokine Netw 12: 462-7 (2001).
58. Zabłocka A, Janusz M, Macała J, Lisowski J. A proline-rich poly-peptide complex (PRP) isolated from ovine colostrum. Modulation of H2O2 and cytokine induction in human leukocytes. Int Immuno-pharmacol 7: 981-8 (2007).
59. Kubis A, Marcinkowska E, Janusz M, Lisowski J. Studies on the mechanism of action of a proline-rich polypeptide complex (PRP): Effect on the stage of cell differentiation. Peptides 26: 2188-92 (2005).
60. Boldogh I, Liebenthal D, Hughes TK, Juelich TL, Georgiades JA, Kruzel ML et al. Modulation of 4HNE-mediated signaling by proline-rich peptides from ovine colostrum. J Mol Neurosci 20: 125-34 (2003).
61. Bacsi A, Stanton GJ, Hughes TK, Kruzel M, Boldogh I. Colos-trinin-driven neurite outgrowth requires p53 activation in PC12 cells. Cell Mol Neurobiol 25: 1123-39 (2005).
62. Bacsi A, Woodberry M, Kruzel ML, Boldogh I. Colostrinin delays the onset of proliferative senescence of diploid murine fibroblast cells. Neuropeptides 41: 93-101 (2007).
63. Basci A, Aguilera-Aguirre L, German P, Kruzel M, Boldogh I. Colostrinin decreased spontaneous and induced mutation frequen-cies at the hprt locus in Chinese hamster V79 cells. J Exp Ther On-col 5: 249-59 (2006).
64. Boldogh I, Aguilera-Aguirre L, Basci A, Choudhury BK, Saavedra-Molina A, Kruzel M. Colostrinin decreases hypersensitivity and al-lergic responses to common allergens. Int Arch Allergy Immunol 146: 298-306 (2008).
65. Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Phys Rev 81: 741-66 (2002).
66. Blasko I, Stampfer-Kountchev M, Robatscher P, Veerhius R, Eikelenboom P, Grubeck-Loebanstein B. How chronic inflamma-tion can affect the brain and support the development of Alz-heimer's disease in old age: the role of microglia and astrocytes. Aging Cell 3: 169-76 (2004).
67. Castelli RJ, Beach TG, Yaari R, Reiman EH. Alzheimer's disease a century later. J Clin Psychiatry 67: 1764-800 (2006).
68. Weiner HL, Frenkel D. Immunology and immunotherapy of Alz-heimer's disease. Nat Rev Immunol 6: 404-16 (2006).
69. Rafii MS, Aisen PS. Recent developments in Alzheimer's disease therapeutics. BMC Med 7: 7 (2009)
70. Fiala M, Cribbs DH, Rosenthal M, Bernard G. Phagocytosis of amyloid-beta and inflammation: two faces of innate immunity in Alzheimer's disease. J Alzheimers Dis 11: 457-63 (2007).
71. Rojo LE, Fernandez AA, Maccioni AA, Jimenez JM, Maccioni RB. Neuro-inflammation: implications for the pathogenesis and mo-lecular diagnosis of Alzheimer's disease. Arch Med Res 39: 1-16 (2008).
72. Maccioni RB, Rojo LE, Fernandez JA, Kuljis RO. The role of neuroimmunomodulation in Alzheimer's disease. Neuroimmuno-modulation: Ann N Y Acad Sci 1153: 240-6 (2009).
73. Rogers J, Strohmeyer R, Kovelovski CJ. Microglia and inflamma-tory mechanisms in the clearance of amyloid beta peptide. Glia 40: 260-9 (2002).
74. Heneka MT, O'Banion MK. Inflammatory processes in Alz-heimer's disease. J Neuroimmunol 184: 69-91 (2007).
75. Eikelenboom P, Veerhuis R, Scheper W, Rozenmuller AJM, van Gool WA, Hoozemans JJM. The significance of neuroinflamma-tion in understanding Alzheimer's disease. J Neural Transm 113: 1685-95 (2006).
76. Medeiros R, Prediger RD, Passos GF, Pandolfo P, Duarte FS, Franco JL, et al. Connecting TNF-alpha signaling pathways to iNOS expression in a mouse model of Alzheimer's disease: rele-vance for the behavioral and synaptic deficits induced by amyloid beta protein. J Neurosci 27: 5394-404 (2007).
77. Steinman L. Nuanced roles of cytokines in three major human brain disorders. J Clin Invest 118: 3557-63 (2008).
78. Orellana DI, Quintanilla RA, Maccioni RB. Neuroprotective effect of TNF alpha against the beta-amyloid neurotoxicity by CDK5 kinase. Biochem Biophys Acta 1773: 254-63 (2007).
79. Shaftel SS, Kyrkanides S, Olschowka JA, Miller JNH, Johnson RE, O'Banion MK. Sustained hippocampal IL-beta overexpression me-diates chronic neuroinflammation and ameliorates Alzheimer plaque pathology. J Clin Invest 117: 1595-604 (2007).
80. Ischiropoulos H, Beckman JS. Oxidative stress and nitration in neurodegeneration cause, effect, or association? J Clin Invest 111: 163-9 (2003).
81. Filipcik P, Cente M, Ferencik M, Hulin I, Novak M. The role of oxidative stress in the pathogenesis of Alzheimer's disease. Bratisl Lek Listy 107: 384-94 (2006).
82. De Felice FG, Velasco PT, Lambert MP, Viola K, Fernandez SJ, Ferreira ST, et al. Abeta oligomers induce neuronal oxidative stress through an N-methyl-D-aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantine. J Biol Chem 282: 11590-601 (2007).
83. Pratico D. Evidence of oxidative stress in Alzheimer's disease brain and antioxidant therapy: lights and shadows. Ann NY Acad Sci 1147: 70-8 (2008).
84. Siegel SJ, Bieschke J, Powers ET, Kelly JW. The oxidative stress metabolite 4-hydroxynonenal promotes Alzheimer protofibril for-mation. Biochemistry 46: 1503-10 (2007).
85. Corzo L, Zas R, Rodriguez S, Cacabelos R. Decreased level of serum nitric oxide in different forms of dementia. Neurosci Lett 420: 263-7 (2007).
86. Small GW, Kaufer D, Mendiondo MS, Quarg P, Spiegel R. Cogni-tive performance in Alzheimer's disease patients receiving rivas-tigmine for up to 5 years. Int J Clin Pract 59: 473-7 (2005).
87. Briks J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev 1:CD005593 (2006).
88. Wallin AK, Andreasen N, Eriksson S, Batsman S, Nasman B, Ekdahl A, et al. Donepezil in Alzheimer's disease: what to expect after 3 years of treatment in a routine clinical setting. Dement Geri-atr Cogn Disord 23: 150-60 (2007).
89. Becker RR, Greig NH. Alzheimer's disease drug development in 2008 and beyond: problems and opportunities. Curr Alzheimer Res 5: 346-57 (2008).
90. Munoz-Torrero D. Acetylocholinesterarse inhibitors as disease-modifying therapies for Alzheimer's disease. Curr Med Chem 15: 2433-55 (2008).
91. Othan G, Orhan I, Subutay-Ozetkin N, Ak F, Sener B. Contempo-rary anticholinesterase pharmaceuticals of natural origin and their synthetic analogues for the treatment of Alzheimer's disease. Re-cent Pat CNS Drug Discov 4: 43-51 (2009).
92. Chu LW, Yik PY, Mok W, Chung CP. A 2-year open-label study of galantamine therapy in Chinese Alzheimer's disease patients in Hong Kong. Int J Clin Pract 61: 403-10 (2007).
93. Feldman HH, Ferris S, Winblad B, Stifkas N, Mancione L, He Y. Effect of rivastigmine on delay to diagnosis of Alzheimer's disease from mild cognitive impairment: the DDEx study. Lancet Neurol 6: 1-12 (2007).
94. Seltzer B. Donepezil: an update. Expert Opin Pharmacother 8: 1011-23 (2007).
95. Winblad B, Machado JC. Use of rivastigmine transdermal patch in the treatment of Alzheimer's disease. Expert Opin Drug Deliv 5: 1377-86 (2008).
96. Ott BR, Blake LM, Kagan E, Resnick M. Open label, multicenter, 28-week extension study of the safety and tolerability of meman-tine in patients with mild to moderate Alzheimer's disease. J Neu-rol 254: 351-8 (2007).
97. Song MS, Rauw G, Baker GB, Kar S. Memantine protects rat cor-tical cultured neurons against beta-amyloid induced toxicity by at-tenuating tau phosphorylation. Eur J Neurosci 28: 1989-2002 (2008).
98. Farlow MR, Cummings JL. Effective pharmacologic management of Alzheimer's disease. Am J Med 120: 388-97 (2007).
99. Hsiung GY, Feldman HH. Pharmacological treatment in moderate-to-severe Alzheimer's disease. Expert Opin Pharmacother 9: 2575-82 (2008).
100. Ancelin ML, Christen Y, Ritchie K. Is antioxidant therapy a viable alternative for mild cognitive impairment? Examination of the evi-dence. Dement Geriatr Cogn Disord 24: 1-19 (2007).
101. Nivsarkar M, Banerjee A, Padh H. Cyclooxygenase inhibitors: a novel direction for Alzheimer's management. Pharmacol Rep 60: 692-8 (2008).
102. Morinaga A, Hirohata M, Ono K, Yamada M. Estrogen has anti-amyloidogenic effect on Alzheimer's beta-amyloid fibrils in vitro. Biochem Biophys Res Commun 359: 697-702 (2007).
103. Christensen DD. Alzheimer's disease: progress in the development of anti-amyloid disease-modifying therapies. CNS Spectr 12: 13-6, 119-23 (2007).
104. Yeon SW, Jeon YJ, Hwang EM, Kim TY. Effects of peptides de-rived from BACE1 catalytic domain on APP processing. Peptides 28: 834-44 (2007).
105. Tomita Y. At the frontline of Alzheimer's disease treatment: -secretase inhibitor/modulator mechanism. Naunyn-Schmiedeberg's Arch Pharmacol 377: 295-300 (2008).
106. Arispe N, Diaz JC, Simakova O. Abeta ion channels. Prospects for treating Alzheimer's disease. BBA -Biomembranes 1768: 1952-65 (2007).
107. Estrada LD, Soto C. Disrupting beta-amyloid aggregation for Alz-heimer disease treatment. Curr Top Med Chem 7: 115-26 (2007).
108. Mandelkow E, Von Bergen M, Pickhardt M, Gazowa Z, Khlistunova I, Wang YP, et al. Tau aggregation and Tau aggregation in-hibitors. J Neurochem 94: 213-214 (2005).
109. Gong CX, Iqbal K. Hyperphosphorylation of microtubule-associated protein tau: a promising therapeutic target for Alzheimer disease. Curr Med Chem 15: 2321-8 (2008).
110. Noble W, Garwood C, Stephenson J, Kinsey AM, Hanger DP, Anderton BH. Monocycline reduces the development of abnormal tau species in models of Alzheimer's disease. FASEB J 23: 739-50 (2009).
111. Oliveira AA Jr, Hodges HM. Alzheimer's disease and neural trans-plantation as prospective cell therapy. Curr Alzheimer Res 2: 79-95 (2005).
112. Feigin A, Eidelberg D. Gene transfer therapy for neurodegenerative disorder. Mov Disord 22: 1223-8 (2007).
113. Tuszynski MN. Nerve growth factor gene therapy in Alzheimer disease. Alzheimer Dis Assoc Disord 21: 179-89 (2007).
114. Lee JK, Jin HK, Bae JS. Bone marrow-derived mesenchymal stem cells reduce brain amyloid-beta deposition and accelerate the acti-vation of microglia in an induced Alzheimer's disease mouse model. Neurosci Lett 450: 136-41 (2009).
115. Feng Z, Zhao G, Yu L. Neural stem cells and Alzheimer's disease; challenges and hope. Am J Alzheimers Dis Other Demen 24: 52-7 (2009).
116. Woodhouse A, Dickson TC, Vickers JC. Vaccination strategies for Alzheimer's disease: A new hope? Drugs Aging 24: 107-19 (2007).
117. Thomas RS, Liddell JE, Murphy LS, Pache DM, Kidd EJ. An anti-body to beta-secretase cleavage site on amyloid-beta protein pre-cursor inhibits amyloid-beta production. J Alzheimers Dis 10: 379-90 (2006).
118. Prada CM, Garcia-Alloza M, Betensky RA, Zhang-Nunes SX, Greenberg SM, Bacskai BJ, et al. Antibody mediated clearance of amyloid-beta peptide from cerebral amyloid angiopathy revealed by quantitative in vivo imaging. J Neurosci 27: 1973-80 (2007).
119. Solomon B. Clinical immunological approaches for the treatment of Alzheimer's disease. Expert Opin Invest Drugs 16: 819-28 (2007).
120. Thakker DR, Weatherspoon MR, Harrison J, Keene TE, Lane DS, Kaemmerer WF, et al. Intracerebroventicular amyloid-beta anti-bodies reduce cerebral amyloid angiopathy and associated micro-hemorrhages in aged Tg257 mice. Proc Natl Acad Sci USA 106: 4501-6 (2009).
121. Okura Y, Matsumoto Y. DNA vaccine therapy for Alzheimer's disease: present status and future direction. Rejuvenation Res 11: 301-8 (2008).
122. Okura Y, Matsumoto Y. Recent advance in immunotherapies for Alzheimer's disease: With special reference to DNA vaccination. Hum Vaccine 5: 373-80 (2009).
123. Napryeyenko O, Borzenko I; GINDEM-NP Study Group. Ginkgo biloba special extract in dementia with neuropsychiatric features. A randomized, placebo-controlled, double-blind clinical trial. Arzneimittelforschung 57: 4-11 (2007).
124. DeKosky ST, Williamson JD, Fitzpatrick AL, Kronmal RA, Ives DG, Saxton JA, et al. Ginkgo Evaluation of Memory (GEM) Study Investigators. JAMA 300: 2253-62 (2008).
125. Augustin S, Rimbach G, Augustin K, Schliebs R, Wolffram S, Cermak R. Effect of short-and long-term treatment with Ginkgo biloba extract on amyloid precursor protein levels in a transgenic model relevant to Alzheimer's disease. Arch Biochem Biophys 481: 177-82 (2009).
126. Mei Z, Zhang F, Tao L, Zheng W, Cao Y, Wang Z, et al. Crypto-tanshinone, a compound from Salvia miltiorrhiza modulates amy-loid precursor protein metabolism and attenuates beta-amyloid deposition through upregulating alpha-secretase in vivo and in vi-tro. Neurosci Lett 452: 90-5 (2009).
127. Ho L, Chen LH, Wang J, Zhao W, Talcott ST, Ono K, et al. Heterogeneity in red wine polyphenolic contents differentially in-fluences Alzheimer's disease-type neuropathology and cognitive deterioration. J Alzheimers Dis 16: 59-72 (2009).
128. Ding Y, Qiao A, Wang Z, Goodwin JS, Lee ES, Block ML, et al. Retinoic acid attenuates beta-amyloid deposition and rescues mem-ory deficits in an Alzheimer's disease transgenic mouse model. J Neurosci 28: 11622-34 (2008).
129. Qing H, He G, Ly PT, Fox CJ, Staufenbiel M, Cai F, et al. Valproic acid inhibit Abeta production, neuritic plaque formation, and be-havioral deficits in Alzheimer's disease mouse models. J Exp Med 205: 2781-9 (2008).
130. Filiz G, Prize KA, Caragounis A, Du T, Crouch PJ, White AR. The role of metals in modulating metalloprotease activity in the AD brain. Eur Biophys J 37: 315-21 (2008).
131. Bica L, Crouch PJ, Cappai R, White AR. Metallo-complex activa-tion of neuroprotective signaling pathways as a therapeutic treat-ment for Alzheimer's disease. Mol Biosyst 5: 134-42 (2009).
132. Banks WA. Developing drugs that can cross the blood-brain bar-rier: applications to Alzheimer's disease. BMC Neurosci 9 (Suppl 3): S2 (2008).
133. Szegedi V, Fülöp L, Farkas T, Rózsa E, Robotka H, Kis Z, et al. Pentapeptides derived from A 1-42 protect neurons from the modulatory effect of A fibrils -an in vitro and in vivo electro-physiological study. Neurobiol Dis 18: 499-508 (2005).
134. Juhás G, Márki A, Vass G, Fülöp L, Budai D, Penke B, et al. An intraperitoneally administered pentapeptide protects against Abeta (1-42) induced neuronal excitation in vivo. J Alzheimers Dis 16: 189-96 (2009).
135. Gozes I, Divinski I, Piltzer I. NAP and D-SAL: neuroprotection against the beta amyloid peptide (1-42). BMC Neurosci (9 Suppl 3): S3 (2008).
136. Popik P, Bobula B, Janusz M, Lisowski J, Vetulani J. Colostrinin, a polypeptide isolated from early milk, facilitates learning, memory in rats. Pharmacol Biochem Behav 64: 183-9 (1999).
137. Popik P, Galoch Z, Janusz M, Lisowski J, Vetulani J. Cognitive effects of Colostral-Val nonapeptide in aged rats. Behav Brain Res 118: 201-8 (2001).
138. Stewart MG, Banks D. Enhancement of long-term memory reten-tion by Colostrinin in one-day-old chicks trained on a weak passive avoidance learning paradigm. Neurobiol Learn Mem 86: 66-71 (2006).
139. TM increases the lifespan and neurological performance of mice. Neurodegener Dis 4 (suppl 1): 264 (2007).
140. Inglot A, Janusz M, Lisowski J. Colostrinine: a proline-rich poly-peptide from ovine colostrum is a modest cytokine inducer in hu-man leukocytes. Arch Immunol Ther Exp 44: 215-24 (1996).
141. Schuster D, Rajendran A, Hui SW, Nicotera T, Srikrishnan T, Kruzel ML. Protective effect of colostrinin on neuroblastoma cell survival is due to reduced aggregation of -amyloid. Neuropeptides 39: 419-26 (2005).
142. Bourhim M, Kruzel M, Srikrishnan T, Nicotera T. Linear quantita-tion of A aggregation using Thioflavin T: Reduction in fibril for-mation by colostrinin. J Neurosci Meth 160: 264-8 (2007).
143. Janusz M, Woszczyna M, Lisowski M, Kubis A, Macała J, Gotszalk T, et al. Ovine colostrum nanopeptide affects amyloid beta aggregation. FEBS Lett 583: 190-6 (2009).
144. ®: a proline-rich polypeptide (PRP) complex isolated from ovine colostrums for treatment of Alz-heimer's disease. A double-blind, placebo-controlled study. Arch Immunol Ther Exp 47: 377-85 (1999).
145. ® proline-rich polypeptide complex from ovine colostrum -a long-term study of its efficacy in Alzheimer's disease. Med Sci Monit 8: P193-6 (2002).
146. Bilikiewicz A, Gaus W. Colostrinin (a naturally occurring, proline-rich, polypeptide mixture) in the treatment of Alzheimer's disease. J Alzheimers Dis 6: 17-26 (2004).
147. Szanislo P, German O, Hajs G, Saenz DN, Woodberry MW, Kruzel ML, et al. Effect of Colostrinin on gene expression-transcriptional network analysis. Int Immunopharmacol 9: 181-93 (2009).
148. TM in Alzheimer's disease. J Nutr Health Aging 13: 235-41 (2009).
149. Zabłocka A, Siednienko J, Mitkiewicz M, Gorczyca WA, Lisowski J, Janusz M. Proline-rich polypeptide complex (PRP) regulates se-cretion of inflammatory mediators by its effect on NF-B activity. Biomed Pharmacother; (2009), (in press) doi: 10.1016/j.biopha. 2009.01.009.