Affiliations: Department of Pathology and Department of Neurosciences, University of Toledo Health Sciences Center, Toledo, OH, USA
Correspondence:
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Correspondence to: Kenneth Hensley, Department of Pathology and Department of Neurosciences, University of Toledo Health Sciences Center, MS 1090, 3000 Arlington Avenue, Toledo, OH 43614-2598, USA. Tel.: +1 419 383 3442; Fax: +1 419 383 3066; E-mail: [email protected].
Abstract: The concept of neuroinflammation has evolved over the past two decades from an initially controversial viewpoint to its present status as a generally accepted idea whose mechanisms and consequences are still actively under research and debate, particularly with regard to Alzheimer's disease (AD). This review summarizes the current status of neuroinflammation research as it specifically relates to AD. Neuroinflammation is discussed mechanistically with emphasis on the role of redox signal transduction linked to the activation of central nervous system-relevant innate immune pathways. Redox signaling is presented both as a causal factor and a consequence of sustained neuroinflammation. Functional relationships are discussed that connect distinct neuroinflammatory components such as cytokines, eicosanoids, classic AD pathology (amyloid plaques and neurofibrillary tangles), and the recently emergent notion of "damage-associated molecular patterns". The interaction of these paracrine factors likely can produce positive as well as negative effects on the AD brain, ranging from plaque clearance by microglia in the short term to glial dysfunction and neuronal compromise if the neuroinflammation is chronically sustained and unmitigated. Recent disappointments in AD clinical trials of anti-inflammatory drugs are discussed with reference to possible explanations and potential avenues for future pharmacological approaches to the disease.
