Microglia Activation and Anti-inflammatory Regulation in Alzheimer's Disease

Overview

Journal Mol Neurobiol

Specialties Molecular Biology
Neurology

Date 2010 Mar 3

PMID 20195797

Citations 81

Authors

Lih-Fen Lue

Yu-Min Kuo

Thomas Beach

Douglas G Walker

Affiliations

Soon will be listed here.

Abstract

Inflammatory regulators, including endogenous anti-inflammatory systems, can down-regulate inflammation thus providing negative feedback. Chronic inflammation can result from imbalance between levels of inflammatory mediators and regulators during immune responses. As a consequence, there are heightened inflammatory responses and irreversible tissue damage associated with many age-related chronic diseases. Alzheimer's disease (AD) brain is marked by prominent inflammatory features, in which microglial activation is the driving force for the elaboration of an inflammatory cascade. How the regulation of inflammation loses its effectiveness during AD pathogenesis remains largely unclear. In this article, we will first review current knowledge of microglial activation and its association with AD pathology. We then discuss four examples of anti-inflammatory systems that could play a role in regulating microglial activation: CD200/CD200 receptor, vitamin D receptor, peroxisome proliferator-activated receptors, and soluble receptor for advanced glycation end products. Through this, we hope to illustrate the diverse aspects of inflammatory regulatory systems in brain and neurodegenerative diseases such as AD. We also propose the importance of neuronal defense systems, because they are part of the integral inflammatory and anti-inflammatory systems. Augmenting the anti-inflammatory defenses of neurons can be included in the strategy for restoration of balanced immune responses during aging and neurodegenerative diseases.

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References

Sheffield L, Berman N . Microglial expression of MHC class II increases in normal aging of nonhuman primates. Neurobiol Aging. 1998; 19(1):47-55. DOI: 10.1016/s0197-4580(97)00168-1. View

Ronnemaa E, Zethelius B, Sundelof J, Sundstrom J, Degerman-Gunnarsson M, Berne C . Impaired insulin secretion increases the risk of Alzheimer disease. Neurology. 2008; 71(14):1065-71. DOI: 10.1212/01.wnl.0000310646.32212.3a. View

Edison P, Archer H, Gerhard A, Hinz R, Pavese N, Turkheimer F . Microglia, amyloid, and cognition in Alzheimer's disease: An [11C](R)PK11195-PET and [11C]PIB-PET study. Neurobiol Dis. 2008; 32(3):412-9. DOI: 10.1016/j.nbd.2008.08.001. View

Henry C, Huang Y, Wynne A, Godbout J . Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1beta and anti-inflammatory IL-10 cytokines. Brain Behav Immun. 2008; 23(3):309-17. PMC: 2692986. DOI: 10.1016/j.bbi.2008.09.002. View

Hoozemans J, Rozemuller J, van Haastert E, Veerhuis R, Eikelenboom P . Cyclooxygenase-1 and -2 in the different stages of Alzheimer's disease pathology. Curr Pharm Des. 2008; 14(14):1419-27. DOI: 10.2174/138161208784480171. View

Gezen-Ak D, Dursun E, Ertan T, Hanagasi H, Gurvit H, Emre M . Association between vitamin D receptor gene polymorphism and Alzheimer's disease. Tohoku J Exp Med. 2007; 212(3):275-82. DOI: 10.1620/tjem.212.275. View

Sohn J, So J, Hong H, Kim J, Na D, Kim M . Identification of autoantibody against beta-amyloid peptide in the serum of elderly. Front Biosci (Landmark Ed). 2009; 14(10):3879-83. DOI: 10.2741/3496. View

Zhang S, Cherwinski H, Sedgwick J, Phillips J . Molecular mechanisms of CD200 inhibition of mast cell activation. J Immunol. 2004; 173(11):6786-93. DOI: 10.4049/jimmunol.173.11.6786. View

Lyons A, Downer E, Crotty S, Nolan Y, Mills K, Lynch M . CD200 ligand receptor interaction modulates microglial activation in vivo and in vitro: a role for IL-4. J Neurosci. 2007; 27(31):8309-13. PMC: 6673084. DOI: 10.1523/JNEUROSCI.1781-07.2007. View

10.

Bechmann I, Nitsch R . Astrocytes and microglial cells incorporate degenerating fibers following entorhinal lesion: a light, confocal, and electron microscopical study using a phagocytosis-dependent labeling technique. Glia. 1997; 20(2):145-54. DOI: 10.1002/(sici)1098-1136(199706)20:2<145::aid-glia6>3.0.co;2-8. View

11.

Monsonego A, Maron R, Zota V, Selkoe D, Weiner H . Immune hyporesponsiveness to amyloid beta-peptide in amyloid precursor protein transgenic mice: implications for the pathogenesis and treatment of Alzheimer's disease. Proc Natl Acad Sci U S A. 2001; 98(18):10273-8. PMC: 56951. DOI: 10.1073/pnas.191118298. View

12.

Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole G . Inflammation and Alzheimer's disease. Neurobiol Aging. 2000; 21(3):383-421. PMC: 3887148. DOI: 10.1016/s0197-4580(00)00124-x. View

13.

Risner M, Saunders A, Altman J, Ormandy G, Craft S, Foley I . Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease. Pharmacogenomics J. 2006; 6(4):246-54. DOI: 10.1038/sj.tpj.6500369. View

14.

Lindberg C, Selenica M, Westlind-Danielsson A, Schultzberg M . Beta-amyloid protein structure determines the nature of cytokine release from rat microglia. J Mol Neurosci. 2005; 27(1):1-12. DOI: 10.1385/JMN:27:1:001. View

15.

DeLuca H, Cantorna M . Vitamin D: its role and uses in immunology. FASEB J. 2001; 15(14):2579-85. DOI: 10.1096/fj.01-0433rev. View

16.

Bsibsi M, Ravid R, Gveric D, van Noort J . Broad expression of Toll-like receptors in the human central nervous system. J Neuropathol Exp Neurol. 2002; 61(11):1013-21. DOI: 10.1093/jnen/61.11.1013. View

17.

Frank M, Barrientos R, Biedenkapp J, Rudy J, Watkins L, Maier S . mRNA up-regulation of MHC II and pivotal pro-inflammatory genes in normal brain aging. Neurobiol Aging. 2005; 27(5):717-22. DOI: 10.1016/j.neurobiolaging.2005.03.013. View

18.

Oudshoorn C, Mattace-Raso F, van der Velde N, Colin E, van der Cammen T . Higher serum vitamin D3 levels are associated with better cognitive test performance in patients with Alzheimer's disease. Dement Geriatr Cogn Disord. 2008; 25(6):539-43. DOI: 10.1159/000134382. View

19.

Eyles D, Smith S, Kinobe R, Hewison M, McGrath J . Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat. 2004; 29(1):21-30. DOI: 10.1016/j.jchemneu.2004.08.006. View

20.

Stahel P, Flierl M, Morgan B, Persigehl I, Stoll C, Conrad C . Absence of the complement regulatory molecule CD59a leads to exacerbated neuropathology after traumatic brain injury in mice. J Neuroinflammation. 2009; 6:2. PMC: 2631471. DOI: 10.1186/1742-2094-6-2. View