UvA-DARE ( Digital Academic Repository ) Targeting Neuroinflammation to Treat Alzheimer ' s Disease

Over the past few decades, research on Alzheimer’s disease (AD) has focused on pathomechanisms linked to two of the major pathological hallmarks of extracellular deposition of beta-amyloid peptides and intraneuronal formation of neurofibrils. Recently, a third disease component, the neuroinflammatory reaction mediated by cerebral innate immune cells, has entered the spotlight, prompted by findings from genetic, pre-clinical, and clinical studies. Various proteins that arise during neurodegeneration, including beta-amyloid, tau, heat shock proteins, and chromogranin, among others, act as dangerassociated molecular patterns, that—upon engagement of pattern recognition receptors—induce inflammatory signaling pathways and ultimately lead to the production and release of immune mediators. These may have beneficial effects but ultimately compromise neuronal function and cause cell death. The current review, assembled by participants of the Chiclana Summer School on & Michael T. Heneka michael.heneka@ukbonn.de 1 Faculty of Medicine, Institute of Neuropathology, University of Freiburg, Freiburg, Germany 2 Department of Neuroscience, Section Medical Physiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands 3 Experimental Neuroinflammation Laboratory, Department of Experimental Medical Sciences, Biomedical Centrum (BMC), Lund University, Lund, Sweden 4 Department of Psychiatry and Psychotherapy, Medical Center University of Freiburg, Faculty of Medicine University of Freiburg, Freiburg, Germany 5 Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA), Département de la Recherche Fondamentale (DRF), Institut de biologie François Jacob, MIRCen, 92260 Fontenay-aux-Roses, France 6 Neurodegenerative Diseases Laboratory, Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud, UMR 9199, F-92260 Fontenay-aux-Roses, France 7 German Center for Neurodegenerative Diseases (DZNE), Sigmund Freud Str. 27, 53127 Bonn, Germany 8 Biomedical Centre, Institute of Innate Immunity, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany 9 Department of Neurosciences, Laboratory for Neurobiology and Gene Therapy, KU Leuven, Leuven, Belgium 10 Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology, University of Bonn Medical Center, Sigmund-Freud Str. 25, 53127 Bonn, Germany 11 Center for Neuroscience (SILS-CNS), Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands 12 Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-Universität ErlangenNürnberg, Erlangen, Germany 13 Vita-Salute San Raffaele University, Milan, Italy 14 In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy 15 Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany 16 Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA 17 Department of Cellular Neurobiology, Zoological Institute, Technische Universität Braunschweig, Braunschweig, Germany 18 Pfizer Deutschland GmbH, Berlin, Germany CNS Drugs (2017) 31:1057–1082 https://doi.org/10.1007/s40263-017-0483-3