Molecular drug targets and therapies for Alzheimer’s disease
详细信息 查看全文
- 作者：Dev Bukhsh Singh (1)
Manish Kumar Gupta (2)
Rajesh Kumar Kesharwani (3)
Mamta Sagar (2)
Seema Dwivedi (4)
Krishna Misra (5) - 关键词：Alzheimer’s disease ; Amyloid β ; Tau protein ; Amyloid precursor protein ; β and Γ ; secretases ; Glycogen synthase kinase ; 3 ; Acyl ; coenzyme A ; cholesterol acyl ; transferase (ACAT)
- 刊名：Translational Neuroscience
- 出版年：2014
- 出版时间：September 2014
- 年：2014
- 卷：5
- 期：3
- 页码：203-217
- 全文大小：1,235 KB
- 参考文献：1. Moreira P.I., Zhu X., Nunomura A., Smith M.A., Perry G., Therapeutic options in Alzheimer’s disease, Expert Rev. Neurother., 2006, 6, 897-10
2. Christensen D.D., Alzheimer’s disease: progress in the development of anti-amyloid disease-modifying therapies, CNS Spectr., 2007, 12, 119-23
3. Hüll M., Berger M., Heneka M., Disease-modifying therapies in Alzheimer’s disease: how far have we come?, Drugs, 2006, 66, 2075-093
4. Papisov M., Belov V., Belova E., Fischman A.J., Fisher R., Wright J.L., et al., Investigation of intrathecal transport of NPT002, a prospective therapeutic based on phage M13, in nonhuman primates, Drug Deliv. Transl. Res., 2012, 2, 210-21
5. Selkoe D.J., Alzheimer’s disease: genes, proteins, and therapy, Physiol. Rev., 2001, 81, 741-66
6. Glenner G.G., Wong C.W., Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein, Biochem. Biophys. Res. Commun., 1984, 120, 885-90
7. Kang J., Lemaire H.G., Unterbeck A., Salbaum J.M., Masters C.L., Grzeschik K.H., et al., The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor, Nature, 1987, 325, 733-36
8. Vetrivel K.S., Thinakaran G., Amyloidogenic processing of betaamyloid precursor protein in intracellular compartments, Neurology, 2006, 66, S69-3
9. Zimmermann M., Gardoni F., Di Luca M., Molecular rationale for the pharmacological treatment of Alzheimer’s disease, Drugs Aging, 2005, 22(Suppl. 1), 27-7
10. Van Marum R.J., Current and future therapy in Alzheimer’s disease, Fundam. Clin. Pharmacol., 2008, 22, 265-74
11. Crouch P.J., Harding S.M., White A.R., Camakaris J., Bush A.I., Masters C.L., Mechanisms of A beta mediated neurodegeneration in Alzheimer’s disease, Int. J. Biochem. Cell Biol., 2008, 40, 181-98
12. Roher A.E., Lowenson J.D., Clarke S., Woods A.S., Cotter R.J., Gowing E., et al., β-Amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease, Proc. Natl. Acad. Sci. USA, 1993, 90, 10836-0840
13. Jarrett J.T., Berger E.P, Lansbury P.T. Jr, The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer’s disease, Biochemistry, 1993, 32, 4693-697
14. Davis-Salinas J., Van Nostrand W.E., Amyloid β-protein aggregation nullifies its pathologic properties in cultured cerebrovascular smooth muscle cells, J. Biol. Chem., 1995, 270, 20887-0890
15. Davis-Salinas J., Saporito-Irwin S.M., Cotman C.W., Van Nostrand W.E. Amyloid β-protein induces its own production in cultured degenerating cerebrovascular smooth muscle cells, J. Neurochem., 1995, 65, 931-34
16. Saito T., Suemoto T., Brouwers N., Sleegers K., Funamoto S., Mihira N., et al., Potent amyloidogenicity and pathogenicity of Aβ43, Nat. Neurosci., 2011, 14, 1023-032
17. Malinchik S.B., Inouye H., Szumowski K.E., Kirschner D.A., Structural analysis of Alzheimer’s beta(1-40) amyloid: protofilament assembly of tubular fibrils, Biophys. J., 1998, 74, 537-45
18. Serpell L.C., Alzheimer’s amyloid fibrils: structure and assembly, Biochim. Biophys. Acta, 2000, 1502, 16-0
19. Tycko R., Insights into the amyloid folding problem from solid-state NMR, Biochemistry, 2003, 42, 3151-59
20. Balbach J.J., Petkova A.T., Oyler N.A., Antzutkin O.N., Gordon D.J., Meredith S.C., et al., Supramolecular structure in full-length Alzheimer’s beta-amyloid fibrils: evidence for a parallel beta-sheet organization from solid-state nuclear magnetic resonance, Biophys. J., 2002, 83,1205-216
21. Antzutkin O.N., Leapman R.D., Balbach J.J., Tycko R., Supramolecular structural constraints on Alzheimer’s beta-amyloid fibrils from electron microscopy and solid-state nuclear magnetic resonance, Biochemistry, 2002, 41, 15436-5450
22. Chiu M.J., Chen Y.F., Chen T.F., Yang S.Y., Yang F.P., Tseng T.W., et al., Plasma tau as a window to the brain-negative associations with brain volume and memory function in mild cognitive impairment and early Alzheimer’s disease, Hum. Brain Mapp., 2014, 35, 3132-142
23. Holmes B.B., Diamond M.I., Prion-like properties of tau protein: the importance of extracellular tau as a therapeutic target, J. Biol. Chem., Epub ahead of print, DOI: jbc.R114.549295
24. Clavaguera F., Akatsu H., Fraser G., Crowther R.A., Frank S., Hench J., et al., Brain homogenates from human tauopathies induce tau inclusions in mouse brain, Proc. Natl. Acad. Sci. USA, 2013, 110, 9535-540
25. Nonaka T., Masuda-Suzukake M., Arai T., Hasegawa Y., Akatsu H., Obi T., et al., Prion-like properties of pathological TDP-43 aggregates from diseased brains, Cell Rep., 2013, 4, 124-34
26. Yanamandra K., Kfoury N., Jiang H., Mahan T.E., Ma S., Maloney S.E., et al., Anti-tau antibodies that block tau aggregate seeding in vitro markedly decrease pathology and improve cognition in vivo, Neuron, 2013, 80, 402-14
27. Meyer-Luehmann M., Coomaraswamy J., Bolmont T., Kaeser S., Schaefer C., Kilger E., et al., Exogenous induction of cerebral betaamyloidogenesis is governed by agent and host, Science, 2006, 313, 1781-784
28. Hensley K., Neuroinflammation in Alzheimer’s disease: mechanisms, pathologic consequences, and potential for therapeutic manipulation, J. Alzheimers Dis., 2010, 21, 1-4
29. Kamat C.D., Gadal S., Mhatra M., Williamson K.S., Pye Q.N., Hensley K., Antioxidants in central nervous system diseases: preclinical promise and translational strategies, J. Alzheimers Dis., 2008, 15, 473-93
30. in t-Veld B.A., Ruitenberg A., Hofman A., Launer L.J., Vn Duijn C.M., Stijnen T., et al., Nonsteroidal anti-inflammatory drugs and the risk of Alzheimer’s disease, N. Engl. J. Med., 2001, 345, 1515-521
31. Ferretti M.T., Allard S., Partridge V., Ducatenzeiler A., Cuello A.C., Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of Alzheimer’s disease-like amyloid pathology, J. Neuroinflammation, 2012, 9, 62
32. Lorenzo A., Yankner B.A., β-amyloid neurotoxicity requires fibril formation and is inhibited by Congo red, Proc. Natl. Acad. Sci. USA., 1994, 91, 12243-2247
33. Soto C., Sigurdsson E.M., Morelli L., Kumar R.A., Casta?o E.M., Frangione B., Beta-sheet breaker peptides inhibit fibrillogenesis in a rat brain model ofamyloidosis: implications for Alzheimer’s therapy, Nat. Med., 1998, 4, 822-26
34. Klunk W.E., Jacob R.F., Mason R.P., Quantifying amyloid β-peptide (Aβ) aggregation using the Congo red-Aβ (CR-Aβ) spectrophotometric assay, Anal. Biochem., 1999, 266, 66-6
35. Inouye H., Kirschner D.A., Alzheimer’s beta-amyloid: insights into fibril formation and structure from Congo red binding, Subcell. Biochem., 2005, 38, 203-24
36. Wu C., Scott J., Shea J.E., Binding of Congo red to amyloid protofibrils of the Alzheimer Aβ(9-40) peptide probed by molecular dynamics simulations, Biophys. J., 2012, 103, 550-57
37. Staderini M., Auli? S., Bartolini M., Ai Tran H.N., González-Ruiz V., Pérez D.I., et al., A fluorescent styrylquinoline with combined therapeutic and diagnostic activities against Alzheimer’s and prion diseases, ACS Med. Chem. Lett., 2013, 4, 225-29
38. McKnight R.E., Jackson D.R., Yokoyama K., Temperature dependence of Congo red binding to amyloid β12-28, Eur. Biophys. J., 2013, 42, 495-01
39. Wang C.C., Huang H.B., Tsay H.J., Shiao M.S., Wu W.J., Cheng Y.C., et al., Characterization of Aβ aggregation mechanism probed by congo red, J. Biomol. Struct. Dyn., 2012, 30, 160-69
40. John V., Tung J., Hom R., Guinn A., Fang L., Gailunas A., et al., Dipeptide inhibitors of β-secretase, US patent 6864240
41. Attanasio F., Convertino M., Magno A., Caflisch A., Corazza A., Haridas H., et al., Carnosine inhibits Aβ(42)aggregation by perturbing the H-bond network in and around the central hydrophobic cluster, Chembiochem, 2013, 14, 583-92
42. Porat Y., Abramowitz A., Gazit E., Inhibition of amyloid fibril formation by polyphenols: structural similarity and aromatic interactions as a common inhibition mechanism., Chem. Biol. Drug Des., 2006, 67, 27-7
43. Masuda M., Suzuki N., Taniguchi S., Oikawa T., Nonaka T., Iwatsubo T., et al., Small molecule inhibitors of alpha-synuclein filament assembly, Biochemistry, 2006, 45, 6085-094
44. Feng Y., Wang X.P., Yang S.G., Wang Y.J., Zhang X., Du X.T., et al., Resveratrol inhibits beta-amyloid oligomeric cytotoxicity but does not prevent oligomer formation, Neurotoxicology, 2009, 30, 986-95
45. Wang J., Ho L., Zhao W., Ono K., Rosensweig C., Chen L., et al., Grapederived polyphenolics prevent Aβ oligomerization and attenuate cognitive deterioration in a mouse model of Alzheimer’s disease, J. Neurosci., 2008, 28, 6388-392
46. Hamaguchi T., Ono K., Yamada M., Review: curcumin and Alzheimer’s disease, CNS Neurosci. Ther., 2010, 16, 285-97
47. Ganguli M., Chandra V., Kamboh M.I., Johnston J.M., Dodge H.H., Thelma B.K., et al., Apolipoprotein E polymorphism and Alzheimer disease: the Indo-US Cross-National Dementia Study, Arch. Neurol., 2000, 57, 824-30
48. Ono K., Hasegawa K., Naiki H., Yamada M., Curcumin has potent antiamyloidogenic effects for Alzheimer’s β-amyloid fibrils in vitro, J. Neurosci. Res., 2004, 75, 742-50
49. Yang F., Lim G.P., Begum A.N., Ubeda O.J., Simmons M.R., Ambegaokar S.S., et al., Curcumin inhibits formation of amyloid β oligomers and fibrils, binds plaques, and reduces amyloid in vivo, J. Biol. Chem., 2005, 280, 5892-901
50. Lim G.P., Chu T., Yang F., Beech W., Frautschy S.A., Cole G.M., The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse, J. Neurosci., 2001, 21, 8370-377
51. Garcia-Alloza M., Borrelli L.A., Rozkalne A., Hyman B.T., Bacskai B.J., Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model, J. Neurochem., 2007, 102,1095-104
52. Singh D.B., Gupta M.K., Kesharwani R.K., Misra K., Comparative docking and ADMET study of some curcumin derivatives and herbal congeners targeting β-amyloid, Netw. Model. Anal. Health Inform. Bioinforma., 2013, 2, 13-7
53. Anand P., Thomas S.G., Kunnumakkara A.B., Sundaram C., Harikumar K.B., Sung B., et al., Biological activities of curcumin and its analogues (congeners) made by man and Mother Nature, Biochem. Pharmacol., 2008, 76, 1590-611
54. Mithu V.S., Sarkar B., Bhowmik D., Das A.K., Chandrakesan M., Maiti S., et al., Curcumin alters the salt bridge-containing turn region in amyloid β(1-42) aggregates, J. Biol. Chem., 2014, 289, 11122-1131
55. Doggui S., Belkacemi A., Paka G.D., Perrotte M., Pi R., Ramassamy C., Curcumin protects neuronal-like cells against acrolein by restoring Akt and redox signaling pathways, Mol. Nutr. Food Res., 2013, 57, 1660-670
56. Cole S.L., Vassar R., BACE1 structure and function in health and Alzheimer’s disease, Curr. Alzheimer Res., 2008, 5, 100-20
57. Sathya M., Premkumar P., Karthick C., Moorthi P., Jayachandran K.S., Anusuyadevi M., BACE1 in Alzheimer’s disease, Clin. Chim. Acta, 2012, 414, 171-78
58. Vassar R., BACE1: the β-secretase enzyme in Alzheimer’s disease, J. Mol. Neurosci., 2004, 23, 105-14
59. Evin G., Zhu A., Holsinger R.M., Masters C.L., Li Q.X., Proteolytic processing of the Alzheimer’s disease amyloid precursor protein in brain and platelets, J. Neurosci. Res., 2003, 74, 386-92
60. Cole S.L., Vassar R., The role of amyloid precursor protein processing by BACE1, the beta-secretase, in Alzheimer disease pathophysiology, J. Biol. Chem., 2008, 283, 29621-9625
61. Cole S.L., Vassar R., The Alzheimer’s disease beta-secretase enzyme, BACE1, Mol. Neurodegener., 2007, 15, 2-2
62. Vassar R., β-Secretase, APP and Aβ in Alzheimer’s disease, Subcell. Biochem., 2005, 38, 79-03
63. Nawrot B., Targeting BACE with small inhibitory nucleic acids -a future for Alzheimer’s disease therapy?, Acta Biochim. Pol., 2004, 51, 431-44
64. Zuo Z., Luo X., Zhu W., Shen J., Shen X., Jiang H., et al., Molecular docking and 3D-QSAR studies on the binding mechanism of statinbased peptidomimetics with beta-secretase, Bioorg. Med. Chem., 2005, 13, 2121-131
65. Hussain I., Hawkins J., Harrison D., Hille C., Wayne G., Cutler L., et al., Oral administration of a potent and selective non-peptidic BACE-1 inhibitor decreases β-cleavage of amyloid precursor protein and amyloid-β production in vivo, J. Neurochem., 2007, 100, 802-09
66. Cheng X., Zhou Y., Gu W., Wu J., Nie A., Cheng J., et al., The selective BACE1 inhibitor VIa reduces amyloid-β production in cell and mouse models of Alzheimer’s disease, J. Alzheimers Dis., 2013, 37, 823-34
67. Paris D., Ganey N.J., Laporte V., Patel N.S., Beaulieu-Abdelahad D., Bachmeier C., et al., Reduction of beta-amyloid pathology by celastrol in a transgenic mouse model of Alzheimer’s disease, J. Neuroinflammation, 2010, 7, 17
68. Ni?o H., García-Pintos I., Rodríguez-Borges J.E., Escobar-Cubiella M., García-Mera X., Prado-Prado F., Review of synthesis, biological assay and QSAR studies of β-secretase inhibitors, Curr. Comput. Aided Drug Des., 2011, 7, 263-75
69. Bali J., Halima S.B., Felmy B., Goodger Z., Zurbriggen S., Rajendran L., Cellular basis of Alzheimer’s disease, Ann. Indian Acad. Neurol., 2010, 13, 89-3
70. Rajendran L., Schneider A., Schlechtingen G., Weidlich S., Ries J., Braxmeier T., et al., Efficient inhibition of the Alzheimer’s disease beta-secretase by membrane targeting, Science, 2008, 320, 520-23
71. Krishnaswamy S., Verdile G., Groth D., Kanyenda L., Martins R.N., The structure and function of Alzheimer’s gamma secretase enzyme complex, Crit. Rev. Clin. Lab. Sci., 2009, 46, 282-01
72. Francis R., McGrath G., Zhang J., Ruddy D.A., Sym M., Apfeld J., et al., aph-1 and pen-2 are required for Notch pathway signaling, Γ-secretase cleavage of βAPP, and presenilin protein accumulation, Dev. Cell, 2002, 3, 85-7
73. Evin G., Sernee M.F., Masters C.L., Inhibition of Γ-secretase as a therapeutic intervention for Alzheimer’s disease: prospects, limitations and strategies, CNS Drugs, 2006, 20, 351-72
74. Guardia-Laguarta C., Pera M., Lleó A., Γ-Secretase as a therapeutic target in Alzheimer’s diseas, Curr. Drug Targets, 2010,11,506-17
75. Sisodia S.S., St George-Hyslop P.H., Γ-Secretase, notch, Aβ and Alzheimer’s disease: where do the presenilins fit in?, Nat. Rev. Neurosci., 2002, 3, 281-90
76. Martinez-Mir A., González-Pérez A., Gayán J., Antúnez C., Marín J., Boada M., et al., Genetic study of neurexin and neuroligin genes in Alzheimer’s disease, J. Alzheimers Dis., 2013, 35, 403-12
77. Doody R.S., Raman R., Farlow M., Iwatsubo T., Vellas B., Joffe S., et al., A phase 3 trial of semagacestat for treatment of Alzheimer’s disease, N. Engl. J. Med., 2013, 369, 341-50
78. Xing S., Shen D., Chen C., Wang J., Liu T., Yu Z., Regulation of neuronal toxicity of β amyloid oligomers by surface ATP synthase, Mol. Med. Rep., 2013, 8, 1689-694
79. Panza F., Solfrizzi V., Frisardi V., Imbimbo B.P., Capurso C., D’Introno A., et al., Beyond the neurotransmitter-focused approach in treating Alzheimer’s disease: drugs targeting β-amyloid and tau protein, Aging Clin. Exp. Res., 2009, 21, 386-06
80. Kerchner G.A., Boxer A.L., Bapineuzumab, Expert Opin. Biol. Ther., 2010, 10, 1121-130
81. Imbimbo B.P., Ottonello S., Frisardi V., Solfrizzi V., Greco A., Seripa D., et al., Solanezumab for the treatment of mild-to-moderate Alzheimer’s disease, Expert Rev. Clin. Immunol., 2012, 8, 135-49
82. Masuda Y., Fukuchi M., Yatagawa T., Tada M., Takeda K., Irie K., et al., Solid-state NMR analysis of interaction sites of curcumin and 42-residue amyloid β-protein fibrils, Bioorg. Med. Chem., 2011, 19, 5967-974
83. Goedert M., Spillantini M.G., Tau gene mutations and neurodegeneration, Biochem. Soc. Symp., 2001, 67, 59-1
84. De la Monte S.M., Brain insulin resistance and deficiency as therapeutic targets in Alzheimer’s disease, Curr. Alzheimer Res., 2012, 9, 35-6
85. Kaidanovich-Beilin O., Woodgett J.R., GSK-3: functional insights from cell biology and animal models, Front. Mol. Neurosci., 2011, 4, 1-5
86. Bertrand J.A., Thieffine S., Vulpetti A., Cristiani C., Valsasina B., Knapp S., et al., Structural characterization of the GSK-3β active site using selective and non-selective ATP-mimetic inhibitors, J. Mol. Biol., 2003, 333, 393-07
87. Saitoh M., Kunitomo J., Kimura E., Iwashita H., Uno Y., Onishi T., et al., 2-{3-[4-(Alkylsulfinyl)phenyl]-1-benzofuran-5-yl}-5-methyl-1,3,4-oxadiazole derivatives as novel inhibitors of glycogen synthase kinase-3β with good brain permeability, J. Med. Chem., 2009, 52, 6270-286
88. Gentile G., Bernasconi G., Pozzan A., Merlo G., Marzorati P., Bamborough P., et al., Identification of 2-(4-pyridyl)thienopyridinones as GSK-3β inhibitors, Bioorg. Med. Chem. Lett., 2011, 21, 4823-827
89. Coffman K, Brodney M, Cook J, Lanyon L, Pandit J, Sakya S, et al., 6-amino-4-(pyrimidin-4-yl)pyridones: novel glycogen synthase kinase-3β inhibitors, Bioorg. Med. Chem. Lett., 2011, 21, 1429-433
90. Stierand K., Rarey M., Drawing the PDB: protein-ligand complexes in two dimensions, Med. Chem. Lett., 2010, 1, 540-45
91. Bhattacharyya R., Kovacs D.M., ACAT inhibition and amyloid beta reduction, Biochim. Biophys. Acta, 2010 1801, 960-65
92. Chang T.Y., Li B.L., Chang C.C., Urano Y., Acyl-coenzyme A: cholesterol acyltransferases, Am. J. Physiol. Endocrinol. Metab., 2009, 297, E1-
93. Huttunen H.J., Puglielli L., Ellis B.C., MacKenzieIngano L.A., Kovacs D.M., Novel N-terminal cleavage of APP precludes Aβ generation in ACAT-defective AC29 cells, J. Mol. Neurosci., 2009, 37, 6-5
94. Huttunen H.J., Peach C., Bhattacharyya R., Barren C., Pettingell W., Hutter-Paier B., et al., Inhibition of acyl-coenzyme A: cholesterolacyltransferase modulates amyloid precursor protein trafficking in the earlysecretory pathway, FASEB J., 2009, 23, 3819-828
95. Puglielli L., Ellis B.C., Ingano L.A., Kovacs D.M., Role of acyl-coenzyme A: cholesterolacyltransferase activity in the processing of the amyloid precursorprotein, J. Mol. Neurosci., 2004, 24, 93-6
96. Huttunen H.J., Greco C., Kovacs D.M., Knockdown of ACAT-1 reduces amyloidogenic processing of APP, FEBS Lett., 2007, 581, 1688-692
97. Huttunen H.J., Kovacs D.M., ACAT as a drug target for Alzheimer’s disease, Neurodegener. Dis., 2008, 5, 212-14
98. Hutter-Paier B., Huttunen H.J., Puglielli L., Eckman C.B., Kim D.Y., Hofmeister A., et al., The ACAT inhibitor CP-113,818 markedly reduces amyloid pathology in a mouse model of Alzheimer’s disease, Neuron, 2004, 44, 227-38
99. Alegret M., Llaverias G., Silvestre J.S., Acyl coenzyme A: cholesterol acyltransferase inhibitors as hypolipidemic and antiatherosclerotic drugs, Methods Find. Exp. Clin. Pharmacol., 2004, 26, 563-86
100. Huttunen H.J., Havas D., Peach C., Barren C., Duller S., Xia W., et al., The acyl-coenzyme A: cholesterol acyltransferase inhibitor CI-1011 reverses diffuse brain amyloid pathology in aged amyloid precursor protein transgenic mice, J. Neuropathol. Exp. Neurol., 2010, 69, 777-88
101. Gouras G.K., Beal M.F., Metal chelator decreases Alzheimer betaamyloid plaques, Neuron, 2001, 30, 641-42
102. Lee J.Y., Friedman J.E., Angel I., Kozak A., Koh J.Y., The lipophilic metal chelator DP-109 reduces amyloid pathology in brains of human β-amyloid precursorprotein transgenic mice, Neurobiol. Aging, 2004, 25, 1315-321
103. Jia J.Y., Zhao Q.H., Liu Y., Gui Y.Z., Liu G.Y., Zhu D.Y., et al., Phase I study on the pharmacokinetics and tolerance of ZT-1, a prodrug of huperzine A, for the treatment of Alzheimer’s disease, Acta Pharmacol. Sin., 2013, 34, 976-82
104. Liang Y.Q., Tang X.C., Comparative effects of huperzine A, donepezil and rivastigmine on cortical acetylcholine level and acetylcholinesterase activity in rats, Neurosci. Lett., 2004, 361, 56-9
105. Ma X., Gang D.R., In vitro production of huperzine A, a promising drug candidate for Alzheimer’s disease, Phytochemistry, 2008, 69, 2022-028
106. McGleenon B.M., Dynan K.B., Passmore A.P., Acetylcholinesterase inhibitors in Alzheimer’s disease, Br. J. Clin. Pharmacol., 1999, 48, 471-80
107. Nasab N.M., Bahrammi M.A., Nikpour M.R., Rahim F., Naghibis S,N., Efficacy of rivastigmine in comparison to ginkgo for treating Alzheimer’s dementia, J. Pak. Med. Assoc., 2012, 62, 677-80
108. Granica S., Kiss A.K., Jarończyk M., Maurin J.K., Mazurek A.P., Czarnocki Z., Synthesis of imperatorin analogs and their evaluation as acetylcholinesterase and butyrylcholinesterase inhibitors, Arch. Pharm. (Weinheim), 2013, 346, 775-82
109. Alt?ntop M.D., Gurkan-Alp A.S., Ozkay Y., Kaplanc?kl? Z.A., Synthesis and biological evaluation of a series of dithiocarbamates as new cholinesterase inhibitors, Arch. Pharm. (Weinheim), 2013, 346, 571-76
110. Altintop M.D., ?zdemir A., Kaplancikli Z.A., Turan-Zitouni G., Temel H.E., ?ift?i G.A., Synthesis and biological evaluation of some pyrazoline derivatives bearing a dithiocarbamate moiety as new cholinesterase inhibitors, Arch. Pharm. (Weinheim), 2013, 346, 189-99
111. Atwood C.S., Scarpa R.C., Huang X., Moir R.D., Jones W.D., Fairlie D.P., et al., Characterization of copper interactions with Alzheimer amyloid β peptides: identification of an attomolar-affinity copper binding site on amyloid β1-42, J. Neurochem., 2000, 75,1219-233
112. Ha C., Ryu J., Park C.B., Metal ions differentially influence the aggregation and deposition of Alzheimer’s β-amyloid on a solid template, Biochemistry, 2007, 46, 6118-125
113. T?ugu V., Karafin A., Palumaa P., Binding of zinc(II) and copper(II) to the full-length Alzheimer’s amyloid-β peptide, J. Neurochem., 2008, 104, 1249-259
114. Bandyopadhyay S., Huang X., Lahiri D.K., Rogers J.T., Novel drug targets based on metallobiology of Alzheimer’s disease, Expert Opin. Ther. Targets, 2010, 14, 1177-197
115. Cherny R.A., Atwood C.S., Xilinas M.E., Gray D.N., Jones W.D., McLean C.A., et al., Treatment with a copper-zinc chelator markedly and rapidly inhibits β-amyloid accumulation in Alzheimer’s disease transgenic mice, Neuron, 2001, 30, 665-76
116. Finefrock A.E., Bush A.I., Doraiswamy P.M., Current status of metals as therapeutic targets in Alzheimer’s disease, J. Am. Geriatr. Soc., 2003, 51, 1143-148
117. Huang X., Atwood C.S., Moir R.D., Hartshorn M.A., Tanzi R.E., Bush A.I., Trace metal contamination initiates the apparent auto-aggregation, amyloidosis, and oligomerization of Alzheimer’s Aβ peptides, J. Biol. Inorg. Chem., 2004, 9, 954-60
118. Mancino A.M., Hindo S.S., Kochi A., Lim M.H., Effects of clioquinol on metal-triggered amyloid-beta aggregation revisited, Inorg. Chem., 2008, 48, 9596-598
119. Cuajungco M.P., Frederickson C.J., Bush A.I., Amyloid-beta metal interaction and metal chelation, Subcell. Biochem., 2005, 38, 235-54
120. Lahiri D.K., Nall C., Promoter activity of the gene encoding the beta-amyloid precursor protein is up-regulated by growth factors, phorbolester, retinoic acid and interleukin-1, Brain Res. Mol. Brain Res., 1995, 32, 233-40
121. Lahiri D.K., Robakis N.K., The promote activity of the gene encoding Alzheimer beta amyloid precursor protein (APP) is regulated by two blocks of upstream sequences, Brain Res. Mol. Brain Res., 1991, 9, 253-57
122. Rogers J.T., Leiter L.M., McPhee J., Cahill C.M., Zhan S.S., Potter H., et al., Translation of the Alzheimer amyloid precursor protein mRNA is up-regulated by interleukin-1 through 50-untranslated region sequences, J. Biol. Chem., 1999, 274, 6421-431
123. Greig N.H., De Micheli E., Holloway H.W., Yu Q-S., Utsuki T., Perry T., et al., The experimental Alzheimer drug phenserine: pharmacokinetics and pharmacodynamics in the rat, Acta Neurol. Scand., 2000, 176, 74-4
124. Shaw K.T.Y., Utsuki T., Rogers J., Yu Q-S., Sambamurti K., Brossi A., et al., Phenserine regulates translation of β-amyloid precursor mRNA by a putative interleukin-1 responsive element, a target for drug development, Proc. Natl. Acad. Sci. USA, 2001, 98, 7605-610
125. Venti A., Giordano T., Eder P., Bush A.I., Lahiri D.K., Greig N.H., et al., The integrated role of desferrioxamine and phenserine targeted to an iron-responsive element in the APP-mRNA 5-untranslated region, Ann. NY Acad. Sci., 2004, 1035, 34-8
126. Bandyopadhyay S., Huang X., Cho H., Greig N.H., Youdim M.B., Rogers J.T., Metal specificity of an iron-responsive element in Alzheimer’s APP mRNA 5-untranslated region, tolerance of SH-SY5Y and H4 neural cells to desferrioxamine, clioquinol, VK-28, and a piperazine chelator, J. Neural. Transm. Suppl., 2006, 71, 237-47
127. Reznichenko L., Amit T., Zheng H., Avramovich-Tirosh Y., Youdim M.B., Weinreb O., et al., Reduction of iron-regulated amyloid precursor protein and β-amyloid peptide by (-)-epigallocatechin-3-gallate in cell cultures: implications for iron chelation in Alzheimer’s disease, J. Neurochem., 2006, 97, 527-36
128. Orgogozo J.M., Gilman S., Dartigues J.F., Laurent B., Puel M., Kirby L.C., et al., Subacute meningoencephalitis in a subset of patients with AD after Aβ42 immunization, Neurology, 2003, 61, 46-4
129. Holmes C., Boche D., Wilkinson D., Yadegarfar G., Hopkins V., Bayer A., et al., Long-term effects of Aβ42 immunisation in Alzheimer’s disease: follow-up of a randomised, placebo-controlled I trial, Lancet, 2008, 372, 216-23
130. Monsonego A., Zota V., Karni A., Krieger J.I., Bar-Or A., Bitan G., et al., Increased T-cell reactivity to amyloid-β protein in older humans and patients with Alzheimer disease, J. Clin. Invest., 2003, 112, 415-22
131. Rask-Andersen M., Almén M.S., Schi?th H.B., Trends in the exploitation of novel drug targets, Nat. Rev. Drug Discov., 2011, 10, 579-90
132. Anus C., Vaccines for Alzheimer’s disease: how close are we?, CNS Drugs, 2003, 17, 457-74
133. Pietrzik C., Behl C., Concepts for the treatment of Alzheimer’s disease: molecular mechanisms and clinical application, Int. J. Exp. Pathol., 2005, 86, 173-85
134. Scarpini E., Scheltens P., Feldman H., Treatment of Alzheimer’s disease: current status and new perspectives, Lancet Neurol., 2003, 2, 539-47
135. Siemers E.R., Dean R.A., Demattos R., May P.C., New pathways in drug discovery for Alzheimer’s disease, Curr. Neurol. Neurosci. Rep., 2006, 6, 372-78
136. Singh D.B., Gupta M.K., Singh D.V., Singh S.K., Misra K., Docking and in silico ADMET studies of noraristeromycin, curcumin and its derivatives with Plasmodium falciparum SAH hydrolase: a molecular drug target against malaria, Interdiscip. Sci., 2013, 5, 1-2
137. Upadhyay J., Misra K., Towards the interaction mechanism of tocopherols and tocotrienols (vitamin E) with selected metabolizing enzymes, Bioinformation, 2009, 3, 326-31
138. Douaud G., Refsum H., de Jager C.A., Jacoby R., Nichols T.E., Smith S.M., Smith A.D., Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment, Proc. Natl. Acad. Sci. USA, 2013, 110, 9523-528
139. Yu Y.J., Watts R.J., Developing therapeutic antibodies for neurodegenerative disease, Neurotherapeutics, 2013, 10, 459-72
140. Watts R.J., Dennis M.S., Bispecific antibodies for delivery into the brain, Curr. Opin. Chem. Biol., 2013, 17, 393-99
141. Yu Y.J., Zhang Y., Kenrick M., Hoyte K., Luk W., Lu Y., et al., Boosting brain uptake of a therapeutic antibody by reducing its affinity for a transcytosis target, Sci. Transl. Med., 2011, 3, 84ra44
142. Bien-Ly N., Yu Y.J., Bumbaca D., Elstrott J., Boswell C.A., Zhang Y., et al., Transferrin receptor (TfR) trafficking determines brain uptake of TfR antibody affinity variants, J. Exp. Med., 2014, 211, 233-44
143. Villeda S.A., Plambeck K.E., Middeldorp J., Castellano J.M., Mosher K.I., Luo J., et al., Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice, Nat. Med., 2014, 20, 659-63
144. Sinha M., Jang Y.C., Oh J., Khong D., Wu E.Y., Manohar R., et al., Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle, Science, 2014, 344, 649-52 - 作者单位：Dev Bukhsh Singh (1)
Manish Kumar Gupta (2)
Rajesh Kumar Kesharwani (3)
Mamta Sagar (2)
Seema Dwivedi (4)
Krishna Misra (5)
1. Department of Biotechnology, Institute of Biosciences and Biotechnology, Chhatrapati Shahu Ji Maharaj University, Kanpur, 208024, Uttar Pradesh, India
2. Department of Bioinformatics, University Institute of Engineering and Technology, Chhatrapati Shahu Ji Maharaj University, Kanpur, 208024, Uttar Pradesh, India
3. Division of Applied Science, Indian Institute of Information Technology, Allahabad, 211012, Uttar Pradesh, India
4. School of Biotechnology, Gautam Buddha University, Greater Noida, 201308, Uttar Pradesh, India
5. Center for Biomedical sciences, SGPGIMS campus, Raebareilly road, Lucknow, Uttar Pradesh, India - ISSN：2081-6936
文摘
Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by normal memory loss and cognitive impairment in humans. Many drug targets and disease-modulating therapies are available for treatment of AD, but none of these are effective enough in reducing problems associated with recognition and memory. Potential drug targets so far reported for AD are β-secretase, Γ-secretase, amyloid beta (Aβ) and Aβ fibrils, glycogen synthase kinase-3 (GSK-3), acyl-coenzyme A: cholesterol acyl-transferase (ACAT) and acetylcholinesterase (AChE). Herbal remedies (antioxidants) and natural metal-chelators have shown a very significant role in reducing the risk of AD, as well as lowering the effect of Aβ in AD patients. Researchers are working in the direction of antisense and stem cell-based therapies for a cure for AD, which mainly depends on the clearance of misfolded protein deposits -including Aβ, tau, and alpha-synuclein. Computational approaches for inhibitor designing, interaction analysis, principal descriptors and an absorption, distribution, metabolism, excretion and toxicity (ADMET) study could speed up the process of drug development with higher efficacy and less chance of failure. This paper reviews the known drugs, drug targets, and existing and future therapies for the treatment of AD.