Therapeutic strategies for Alzheimer's disease

被引:162
作者
Wolfe, MS [1 ]
机构
[1] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/nrd938
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Alzheimer's disease is a progressive and ultimately fatal neurological disorder for which there is no effective treatment at present. The disease is characterized pathologically by cerebral plaques that contain the amyloid-beta peptide and thread-like neuronal structures composed of the microtubule-associated protein TAU. Both amyloid-beta and TAU are thought to be crucial to pathogenesis, but compelling evidence supports amyloid-beta as the prime mover'. The main efforts for developing therapeutics are therefore focused on preventing amyloid-beta production, aggregation or downstream neurotoxic events. The progress of these and other approaches raises the hope that effective agents for the prevention and treatment of Alzheimer's disease will be available in the near future.
引用
收藏
页码:859 / 866
页数:8
相关论文
共 97 条
  • [1] Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease
    Bard, F
    Cannon, C
    Barbour, R
    Burke, RL
    Games, D
    Grajeda, H
    Guido, T
    Hu, K
    Huang, JP
    Johnson-Wood, K
    Khan, K
    Kholodenko, D
    Lee, M
    Lieberburg, I
    Motter, R
    Nguyen, M
    Soriano, F
    Vasquez, N
    Weiss, K
    Welch, B
    Seubert, P
    Schenk, D
    Yednock, T
    [J]. NATURE MEDICINE, 2000, 6 (08) : 916 - 919
  • [2] Familial Alzheimer's disease-linked presenilin 1 variants elevate A beta 1-42/1-40 ratio in vitro and in vivo
    Borchelt, DR
    Thinakaran, G
    Eckman, CB
    Lee, MK
    Davenport, F
    Ratovitsky, T
    Prada, CM
    Kim, G
    Seekins, S
    Yager, D
    Slunt, HH
    Wang, R
    Seeger, M
    Levey, AI
    Gandy, SE
    Copeland, NG
    Jenkins, NA
    Price, DL
    Younkin, SG
    [J]. NEURON, 1996, 17 (05) : 1005 - 1013
  • [3] The galvanization of β-amyloid in Alzheimer's disease
    Bush, AI
    Tanzi, RE
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (11) : 7317 - 7319
  • [4] PROTEIN-PHOSPHORYLATION INHIBITS PRODUCTION OF ALZHEIMER AMYLOID-BETA/A4 PEPTIDE
    BUXBAUM, JD
    KOO, EH
    GREENGARD, P
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (19) : 9195 - 9198
  • [5] BACE1 is the major β-secretase for generation of Aβ peptides by neurons
    Cai, HB
    Wang, YS
    McCarthy, D
    Wen, HJ
    Borchelt, DR
    Price, DL
    Wong, PC
    [J]. NATURE NEUROSCIENCE, 2001, 4 (03) : 233 - 234
  • [6] The proteolytic fragments of the Alzheimer's disease-associated presenilin-1 form heterodimers and occur as a 100-150-kDa molecular mass complex
    Capell, A
    Grünberg, J
    Pesold, B
    Diehlmann, A
    Citron, M
    Nixon, R
    Beyreuther, K
    Selkoe, DJ
    Haass, C
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (06) : 3205 - 3211
  • [7] EARLY-ONSET ALZHEIMERS-DISEASE CAUSED BY MUTATIONS AT CODON-717 OF THE BETA-AMYLOID PRECURSOR PROTEIN GENE
    CHARTIERHARLIN, MC
    CRAWFORD, F
    HOULDEN, H
    WARREN, A
    HUGHES, D
    FIDANI, L
    GOATE, A
    ROSSOR, M
    ROQUES, P
    HARDY, J
    MULLAN, M
    [J]. NATURE, 1991, 353 (6347) : 844 - 846
  • [8] Treatment with a copper-zinc chelator markedly and rapidly inhibits β-amyloid accumulation in Alzheimer's disease transgenic mice
    Cherny, RA
    Atwood, CS
    Xilinas, ME
    Gray, DN
    Jones, WD
    McLean, CA
    Barnham, KJ
    Volitakis, I
    Fraser, FW
    Kim, YS
    Huang, XD
    Goldstein, LE
    Moir, RD
    Lim, JT
    Beyreuther, K
    Zheng, H
    Tanzi, RE
    Masters, CL
    Bush, AI
    [J]. NEURON, 2001, 30 (03) : 665 - 676
  • [9] Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice
    Citron, M
    Westaway, D
    Xia, WM
    Carlson, G
    Diehl, T
    Levesque, G
    JohnsonWood, K
    Lee, M
    Seubert, P
    Davis, A
    Kholodenko, D
    Motter, R
    Sherrington, R
    Perry, B
    Yao, H
    Strome, R
    Lieberburg, I
    Rommens, J
    Kim, S
    Schenk, D
    Fraser, P
    Hyslop, PS
    Selkoe, DJ
    [J]. NATURE MEDICINE, 1997, 3 (01) : 67 - 72
  • [10] PROTECTIVE EFFECT OF APOLIPOPROTEIN-E TYPE-2 ALLELE FOR LATE-ONSET ALZHEIMER-DISEASE
    CORDER, EH
    SAUNDERS, AM
    RISCH, NJ
    STRITTMATTER, WJ
    SCHMECHEL, DE
    GASKELL, PC
    RIMMLER, JB
    LOCKE, PA
    CONNEALLY, PM
    SCHMADER, KE
    SMALL, GW
    ROSES, AD
    HAINES, JL
    PERICAKVANCE, MA
    [J]. NATURE GENETICS, 1994, 7 (02) : 180 - 184