Neuroinflammation: a potential therapeutic target

被引:95
作者
Craft, JM [1 ]
Watterson, DM [1 ]
Van Eldik, LJ [1 ]
机构
[1] Northwestern Univ, Ctr Drug Discovery & Chem Biol, Feinberg Sch Med, Chicago, IL 60611 USA
关键词
Alzheimer's disease (AD); drug discovery; multiple sclerosis; natural product; neuroinflammation; nonsteroidal anti-inflammarory drug (NSAID); Parkinson's disease (PD); peroxisome proliferator-activated receptor gamma (PPAR gamma); pyridazine;
D O I
10.1517/14728222.9.5.887
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The increased appreciation of the importance of glial cell-propagated inflammation (termed 'neuroinflammation') in the progression of pathophysiology for diverse neurodegenerative diseases, has heightened interest in the rapid discovery of neuroinflammation-targeted therapeutics. Efforts include searches among existing drugs approved for other uses, as well as development of novel synthetic compounds that selectively downregulate neuroinflammatory responses. The use of existing drugs to target neuroinflammation has largely met with failure due to lack of efficacy or untoward side effects. However, the de novo development of new classes of therapeutics based on targeting selective aspects of glia activation pathways and glia-mediated pathophysiologies, versus targeting pathways of quantitative importance in non-CNS inflammatory responses, is yielding promising results in preclinical animal models. The authors briefly review selected clinical and preclinical data that reflect the prevailing approaches targeting neuroinflammation as a pathophysiological process contributing to onset or progression of neurodegenerative diseases. The authors conclude with opinions based on recent experimental proofs of concept using preclinical animal models of pathophysiology. The focus is on Alzheimer's disease, but the concepts are transferrable to other neurodegenerative disorders with an inflammatory component.
引用
收藏
页码:887 / 900
页数:14
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共 118 条
  • [61] Inhibition of p38 MAP kinase as a therapeutic strategy
    Lee, JC
    Kumar, S
    Griswold, DE
    Underwood, DC
    Votta, BJ
    Adams, JL
    [J]. IMMUNOPHARMACOLOGY, 2000, 47 (2-3): : 185 - 201
  • [62] AN ANTIDIABETIC THIAZOLIDINEDIONE IS A HIGH-AFFINITY LIGAND FOR PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA(PPAR-GAMMA)
    LEHMANN, JM
    MOORE, LB
    SMITHOLIVER, TA
    WILKISON, WO
    WILLSON, TM
    KLIEWER, SA
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (22) : 12953 - 12956
  • [63] EFFECTS OF MELATONIN ON HUMAN MOOD AND PERFORMANCE
    LIEBERMAN, HR
    WALDHAUSER, F
    GARFIELD, G
    LYNCH, HJ
    WURTMAN, RJ
    [J]. BRAIN RESEARCH, 1984, 323 (02) : 201 - 207
  • [64] Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer's disease
    Lim, GP
    Yang, F
    Chu, T
    Chen, P
    Beech, W
    Teter, B
    Tran, T
    Ubeda, O
    Ashe, KH
    Frautschy, SA
    Cole, GM
    [J]. JOURNAL OF NEUROSCIENCE, 2000, 20 (15) : 5709 - 5714
  • [65] The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse
    Lim, GP
    Chu, T
    Yang, FS
    Beech, W
    Frautschy, SA
    Cole, GM
    [J]. JOURNAL OF NEUROSCIENCE, 2001, 21 (21) : 8370 - 8377
  • [66] Cirrhosis and chronic hepatitis -: Letter from the guest Editor
    Martínez-Noguera, A
    [J]. SEMINARS IN ULTRASOUND CT AND MRI, 2002, 23 (01) : 1 - 2
  • [67] Inflammation and the degenerative diseases of aging
    McGeer, PL
    McGeer, EG
    [J]. PROTECTIVE STRATEGIES FOR NEURODEGENERATIVE DISEASES, 2004, 1035 : 104 - 116
  • [68] Inflammation and neurodegeneration in Parkinson's disease
    McGeer, PL
    McGeer, EG
    [J]. PARKINSONISM & RELATED DISORDERS, 2004, 10 : S3 - S7
  • [69] Polymorphisms in inflammatory genes and the risk of Alzheimer disease
    McGeer, PL
    McGeer, EG
    [J]. ARCHIVES OF NEUROLOGY, 2001, 58 (11) : 1790 - 1792
  • [70] Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: A review of 17 epidemiologic studies
    McGeer, PL
    Schulzer, M
    McGeer, EG
    [J]. NEUROLOGY, 1996, 47 (02) : 425 - 432