Microglia activation and anti-inflammatory regulation in Alzheimer's disease.
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.
Lue
Lih-Fen
LF
Laboratory of Neuroregeneration, Banner Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85351, USA. lihfen.lue@bannerhealth.com
Kuo
Yu-Min
YM
Beach
Thomas
T
Walker
Douglas G
DG
D000544:Alzheimer Disease / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D017628:Microglia / Q000166:cytology / Q000502:physiology*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; D015415:Biomarkers; D047495:PPAR gamma; D000067759:Receptor for Advanced Glycation End Products; D018167:Receptors, Calcitriol; D011971:Receptors, Immunologic; C042739:antigens, CD200