| Literature DB >> 25792098 |
Michael T Heneka1, Monica J Carson2, Joseph El Khoury3, Gary E Landreth4, Frederic Brosseron5, Douglas L Feinstein6, Andreas H Jacobs7, Tony Wyss-Coray8, Javier Vitorica9, Richard M Ransohoff10, Karl Herrup11, Sally A Frautschy12, Bente Finsen13, Guy C Brown14, Alexei Verkhratsky15, Koji Yamanaka16, Jari Koistinaho17, Eicke Latz18, Annett Halle19, Gabor C Petzold20, Terrence Town21, Dave Morgan22, Mari L Shinohara23, V Hugh Perry24, Clive Holmes25, Nicolas G Bazan26, David J Brooks27, Stéphane Hunot28, Bertrand Joseph29, Nikolaus Deigendesch30, Olga Garaschuk31, Erik Boddeke32, Charles A Dinarello33, John C Breitner34, Greg M Cole12, Douglas T Golenbock35, Markus P Kummer36.
Abstract
Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.Entities:
Mesh：
Substances：
Year: 2015 PMID： 25792098 PMCID： PMC5909703 DOI： 10.1016/S1474-4422(15)70016-5
Source DB: PubMed Journal: Lancet Neurol ISSN： 1474-4422 Impact factor: 44.182