Current therapeutic targets for the treatment of Alzheimer's disease

被引:62
作者
Grill, Joshua D. [1 ]
Cummings, Jeffrey L. [1 ]
机构
[1] Univ Calif Los Angeles, David Geffen Sch Med, Deane F Johnson Ctr Neurotherapeut, Mary S Easton Ctr Alzheimers Dis Res,Dept Neurol, Los Angeles, CA 90095 USA
关键词
amyloid-beta; beta-secretase; gamma-secretase; Alzheimer's disease; dementia; immunotherapy; tau; therapeutic; treatment; AMYLOID-BETA-PEPTIDE; CYCLIN-DEPENDENT KINASE-5; GAMMA-SECRETASE INHIBITOR; PLACEBO-CONTROLLED TRIAL; HISTAMINE H-3 RECEPTOR; LONG-TERM POTENTIATION; TRANSGENIC MOUSE MODEL; GLYCATION END-PRODUCTS; BLOOD-BRAIN-BARRIER; FACTOR GENE-THERAPY;
D O I
10.1586/ERN.10.29
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Alzheimer's disease is a progressive neurodegenerative disease for which no cure exists. There is a substantial need for new therapies that offer improved symptomatic benefit and disease-slowing capabilities. In recent decades there has been substantial progress in understanding the molecular and cellular changes associated with Alzheimer's disease pathology. This has resulted in identification of a large number of new drug targets. These targets include, but are not limited to, therapies that aim to prevent production of or remove the amyloid-beta protein that accumulates in neuritic plaques; to prevent the hyperphosphorylation and aggregation into paired helical filaments of the microtubule-associated protein tau; and to keep neurons alive and functioning normally in the face of these pathologic challenges. We provide a review of these targets for drug development.
引用
收藏
页码:711 / 728
页数:18
相关论文
共 293 条
[1]   A Phase II study targeting amyloid-β with 3APS in mild-to-moderate Alzheimer disease [J].
Aisen, P. S. ;
Saumier, D. ;
Briand, R. ;
Laurin, J. ;
Gervais, F. ;
Tremblay, P. ;
Garceau, D. .
NEUROLOGY, 2006, 67 (10) :1757-1763
[2]   Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression - A randomized controlled trial [J].
Aisen, PS ;
Schafer, KA ;
Grundman, M ;
Pfeiffer, E ;
Sano, M ;
Davis, KL ;
Farlow, MR ;
Jin, S ;
Thomas, RG ;
Thal, LJ .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2003, 289 (21) :2819-2826
[3]  
ALBRIGHT C, 2008, INT C ALZH DIS CHIC
[4]   A 24-week, double-blind, placebo-controlled study of three dosages of Cerebrolysin in patients with mild to moderate Alzheimer's disease [J].
Alvarez, XA ;
Cacabelos, R ;
Laredo, M ;
Couceiro, V ;
Sampedro, C ;
Varela, M ;
Corzo, L ;
Fernandez-Novoa, L ;
Vargas, M ;
Aleixandre, M ;
Linares, C ;
Granizo, E ;
Muresanu, D ;
Moessler, H .
EUROPEAN JOURNAL OF NEUROLOGY, 2006, 13 (01) :43-54
[5]   Selective cognitive dysfunction in acetylcholine M1 muscarinic receptor mutant mice [J].
Anagnostaras, SG ;
Murphy, GG ;
Hamilton, SE ;
Mitchell, SL ;
Rahnama, NP ;
Nathanson, NM ;
Silva, AJ .
NATURE NEUROSCIENCE, 2003, 6 (01) :51-58
[6]   Is the therapeutic application of neurotrophic factors dead? [J].
Apfel, SC .
ANNALS OF NEUROLOGY, 2002, 51 (01) :8-11
[7]   Caffeine protects Alzheimer's mice against cognitive impairment and reduces brain β-amyloid production [J].
Arendash, G. W. ;
Schleif, W. ;
Rezai-Zadeh, K. ;
Jackson, E. K. ;
Zacharia, L. C. ;
Cracchiolo, J. R. ;
Shippy, D. ;
Tan, J. .
NEUROSCIENCE, 2006, 142 (04) :941-952
[8]   Caffeine Reverses Cognitive Impairment and Decreases Brain Amyloid-β Levels in Aged Alzheimer's Disease Mice [J].
Arendash, Gary W. ;
Mori, Takashi ;
Cao, Chuanhai ;
Mamcarz, Malgorzata ;
Runfeldt, Melissa ;
Dickson, Alexander ;
Rezai-Zadeh, Kavon ;
Tan, Jun ;
Citron, Bruce A. ;
Lin, Xiaoyang ;
Echeverria, Valentina ;
Potter, Huntington .
JOURNAL OF ALZHEIMERS DISEASE, 2009, 17 (03) :661-680
[9]   PAIRED HELICAL FILAMENT-LIKE PHOSPHORYLATION OF TAU, DEPOSITION OF BETA/A4-AMYLOID AND MEMORY IMPAIRMENT IN RAT INDUCED BY CHRONIC INHIBITION OF PHOSPHATASE-1 AND PHOSPHATASE-2A [J].
ARENDT, T ;
HOLZER, M ;
FRUTH, R ;
BRUCKNER, MK ;
GARTNER, U .
NEUROSCIENCE, 1995, 69 (03) :691-698
[10]   NEUROFIBRILLARY TANGLES BUT NOT SENILE PLAQUES PARALLEL DURATION AND SEVERITY OF ALZHEIMERS-DISEASE [J].
ARRIAGADA, PV ;
GROWDON, JH ;
HEDLEYWHYTE, ET ;
HYMAN, BT .
NEUROLOGY, 1992, 42 (03) :631-639