Microglia and Astrocytes in Alzheimer's Disease: Implications for Therapy

被引:387
作者
Fakhoury, Marc [1 ]
机构
[1] Univ Montreal, Fac Med, Dept Neurosci, Montreal, PQ, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
Alzheimer's disease; astrocytes; cytokines; glial cells; inflammation; microglia; MESENCHYMAL STEM-CELLS; NECROSIS-FACTOR-ALPHA; POLARIZING M1 MACROPHAGES; ACTIVATED RECEPTOR-GAMMA; ANTIGEN-PRESENTING CELLS; TRANSGENIC TG2576 MICE; NF-KAPPA-B; AMYLOID-BETA; MOUSE MODEL; IN-VITRO;
D O I
10.2174/1570159X15666170720095240
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the progressive loss of neurons, which typically leads to severe impairments in cognitive functions including memory and learning. Key pathological features of this disease include the deposition of highly insoluble amyloid beta peptides and the formation of neurofibrillary tangles (NFTs) in the brain. Mounting evidence also implicates sustained glial-mediated inflammation as a major contributor of the neurodegenerative processes and cognitive deficits observed in AD. Methods: This paper provides an overview of findings from both human and animal studies investigating the role of microglia and astrocytes in AD, and discusses potential avenues for therapeutic intervention. Results: Glial-mediated inflammation is a 'double-edged sword', performing both detrimental and beneficial functions in AD. Despite tremendous effort in elucidating the molecular and cellular mechanisms underlying AD pathology, to date, there is no treatment that could prevent or cure this disease. Current treatments are only useful in slowing down the progression of AD and helping patients manage some of their behavioral and cognitive symptoms. Conclusion: A better understanding of the role of microglia and astrocytes in the regulation of AD pathology is needed as this could pave the way for new therapeutic strategies.
引用
收藏
页码:508 / 518
页数:11
相关论文
共 158 条
[1]   Astrocyte-endothelial interactions at the blood-brain barrier [J].
Abbott, NJ ;
Rönnbäck, L ;
Hansson, E .
NATURE REVIEWS NEUROSCIENCE, 2006, 7 (01) :41-53
[2]   Astrocyte-endothelial interactions and blood-brain barrier permeability [J].
Abbott, NJ .
JOURNAL OF ANATOMY, 2002, 200 (06) :629-638
[3]   Neuroinflammation, Oxidative Stress and the Pathogenesis of Alzheimer's Disease [J].
Agostinho, Paula ;
Cunha, Rodrigo A. ;
Oliveira, Catarina .
CURRENT PHARMACEUTICAL DESIGN, 2010, 16 (25) :2766-2778
[4]   A randomized controlled trial of prednisone in Alzheimer's disease [J].
Aisen, PS ;
Davis, KL ;
Berg, JD ;
Schafer, K ;
Campbell, K ;
Thomas, RG ;
Weiner, MF ;
Farlow, MR ;
Sano, M ;
Grundman, M ;
Thal, LJ .
NEUROLOGY, 2000, 54 (03) :588-593
[5]   Randomized pilot study of nimesulide treatment in Alzheimer's disease [J].
Aisen, PS ;
Schmeidler, J ;
Pasinetti, GM .
NEUROLOGY, 2002, 58 (07) :1050-1054
[6]  
Aloisi F, 1997, J IMMUNOL, V159, P1604
[7]  
Alzheimer A., 1910, BEITRAGE KENNTNIS PA, P401
[8]   Aging-related down-regulation of neprilysin, a putative β-amyloid-degrading enzyme, in transgenic Tg2576 Alzheimer-like mouse brain is accompanied by an astroglial upregulation in the vicinity of β-amyloid plaques [J].
Apelt, J ;
Ach, K ;
Schliebs, R .
NEUROSCIENCE LETTERS, 2003, 339 (03) :183-186
[9]   β-Amyloid-induced glial expression of both pro- and anti-inflammatory cytokines in cerebral cortex of aged transgenic Tg2576 mice with Alzheimer plaque pathology [J].
Apelt, J ;
Schliebs, R .
BRAIN RESEARCH, 2001, 894 (01) :21-30
[10]   Thrombin and prothrombin are expressed by neurons and glial cells and accumulate in neurofibrillary tangles in Alzheimer disease brain [J].
Arai, T ;
Miklossy, J ;
Klegeris, A ;
Guo, JP ;
McGeer, PL .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2006, 65 (01) :19-25