Anti-inflammatory actions of peroxisome proliferator-activated receptor gamma agonists in Alzheimer's disease

被引:160
作者
Landreth, GE [1 ]
Heneka, MT
机构
[1] Case Western Reserve Univ, Sch Med, Dept Neurosci, Alzheimer Res Lab, Cleveland, OH 44106 USA
[2] Univ Bonn, Dept Neurol, D-53105 Bonn, Germany
关键词
Alzheimer's disease; NSAIDs; inflammation; microglia; peroxisome proliferator-activated receptors; cyclooxygenases;
D O I
10.1016/S0197-4580(01)00296-2
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
The role of inflammatory processes in the brains of Alzheimer's Disease (AD) patients has recently attracted considerable interest. Indeed, the only demonstrated effective therapy for AD patients is long-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs). The mechanistic basis of the efficacy of NSAIDs in AD remains unclear. However, the recent recognition that NSAIDs can bind to and activate the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR gamma), has offered an explanation for the action of these drugs in AD. PPAR gamma activation leads to the inhibition of microglial activation and the expression of a broad range of proinflammatory molecules. The newly appreciated anti-inflammatory actions of PPAR gamma agonists may allow novel therapies for AD and other CNS indications with an inflammatory component. (C) 2001 Elsevier Science Inc. All fights reserved.
引用
收藏
页码:937 / 944
页数:8
相关论文
共 73 条
  • [1] Inflammation and Alzheimer's disease
    Akiyama, H
    Barger, S
    Barnum, S
    Bradt, B
    Bauer, J
    Cole, GM
    Cooper, NR
    Eikelenboom, P
    Emmerling, M
    Fiebich, BL
    Finch, CE
    Frautschy, S
    Griffin, WST
    Hampel, H
    Hull, M
    Landreth, G
    Lue, LF
    Mrak, R
    Mackenzie, IR
    McGeer, PL
    O'Banion, MK
    Pachter, J
    Pasinetti, G
    Plata-Salaman, C
    Rogers, J
    Rydel, R
    Shen, Y
    Streit, W
    Strohmeyer, R
    Tooyoma, I
    Van Muiswinkel, FL
    Veerhuis, R
    Walker, D
    Webster, S
    Wegrzyniak, B
    Wenk, G
    Wyss-Coray, T
    [J]. NEUROBIOLOGY OF AGING, 2000, 21 (03) : 383 - 421
  • [2] Reduced prevalence of AD in users of NSAIDs and H2 receptor antagonists - The Cache County Study
    Anthony, JC
    Breitner, JCS
    Zandi, PP
    Meyer, MR
    Jurasova, I
    Norton, MC
    Stone, SV
    [J]. NEUROLOGY, 2000, 54 (11) : 2066 - 2071
  • [3] Microglial interaction with β-amyloid:: Implications for the pathogenesis of Alzheimer's disease
    Bamberger, ME
    Landreth, GE
    [J]. MICROSCOPY RESEARCH AND TECHNIQUE, 2001, 54 (02) : 59 - 70
  • [4] Role of the peroxisome proliferator-activated receptor-γ (PPAR-γ) and its natural ligand 15-deoxy-Δ12,14-prostaglandin J2 in the regulation of microglial functions
    Bernardo, A
    Levi, G
    Minghetti, L
    [J]. EUROPEAN JOURNAL OF NEUROSCIENCE, 2000, 12 (07) : 2215 - 2223
  • [5] Orphan nuclear receptors - new ligands and new possibilities
    Blumberg, B
    Evans, RM
    [J]. GENES & DEVELOPMENT, 1998, 12 (20) : 3149 - 3155
  • [6] Bornemann KD, 2001, AM J PATHOL, V158, P63, DOI 10.1016/S0002-9440(10)63945-4
  • [7] Breitner JCS, 1996, ANNU REV MED, V47, P401
  • [8] INVERSE ASSOCIATION OF ANTIINFLAMMATORY TREATMENTS AND ALZHEIMERS-DISEASE - INITIAL RESULTS OF A COTWIN CONTROL STUDY
    BREITNER, JCS
    GAU, BA
    WELSH, KA
    PLASSMAN, BL
    MCDONALD, WM
    HELMS, MJ
    ANTHONY, JC
    [J]. NEUROLOGY, 1994, 44 (02) : 227 - 232
  • [9] Anti-inflammatory drugs protect against Alzheimer disease at low doses
    Broe, GA
    Grayson, DA
    Creasey, HM
    Waite, LM
    Casey, BJ
    Bennett, HP
    Brooks, WS
    Halliday, GM
    [J]. ARCHIVES OF NEUROLOGY, 2000, 57 (11) : 1586 - 1591
  • [10] Chattopadhyay N, 2000, J NEUROSCI RES, V61, P67, DOI 10.1002/1097-4547(20000701)61:1<67::AID-JNR8>3.0.CO