title: Chronic neuroinflammation in Alzheimer's disease: new perspectives on animal models and promising candidate drugs.
abstract: Chronic neuroinflammation is now considered one of the major factors in the pathogenesis of Alzheimer's disease (AD). However, the most widely used transgenic AD models (overexpressing mutated forms of amyloid precursor protein, presenilin, and/or tau) do not demonstrate the degree of inflammation, neurodegeneration (particularly of the cholinergic system), and cognitive decline that is comparable with the human disease. Hence a more suitable animal model is needed to more closely mimic the resulting cognitive decline and memory loss in humans in order to investigate the effects of neuroinflammation on neurodegeneration. One of these models is the glial fibrillary acidic protein-interleukin 6 (GFAP-IL6) mouse, in which chronic neuroinflammation triggered constitutive expression of the cytokine interleukin-6 (IL-6) in astrocytes. These transgenic mice show substantial and progressive neurodegeneration as well as a decline in motor skills and cognitive function, starting from 6 months of age. This animal model could serve as an excellent tool for drug discovery and validation in vivo. In this review, we have also selected three potential anti-inflammatory drugs, curcumin, apigenin, and tenilsetam, as candidate drugs, which could be tested in this model.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 2751, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Millington
authors.affiliation: Department of Pharmacology, School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 2751, Australia.
authors.forename: Sandra
authors.identifier: 0000-0002-4841-0151
authors.initials: S
authors.lastname: Sonego
authors.affiliation: Department of Pharmacology, School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 2751, Australia.
authors.forename: Niloo
authors.identifier: 0000-0002-8798-0990
authors.initials: N
authors.lastname: Karunaweera
authors.affiliation: Department of Pharmacology, School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 2751, Australia.
authors.forename: Alejandra
authors.identifier: 0000-0001-6536-6263
authors.initials: A
authors.lastname: Rangel
authors.affiliation: Department of Pharmacology, School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 2751, Australia ; Nanoscale Organisation and Dynamics Group, School of Science and Health, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 2751, Australia.
authors.forename: Janice R
authors.initials: JR
authors.lastname: Aldrich-Wright
authors.affiliation: School of Molecular Bioscience and the Bosch Institute, University of Sydney, Camperdown, NSW 2006, Australia.
authors.forename: Iain L
authors.initials: IL
authors.lastname: Campbell
authors.affiliation: Department of Pharmacology, School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 2751, Australia.
authors.forename: Erika
authors.identifier: 0000-0001-7371-7385
authors.initials: E
authors.lastname: Gyengesi
authors.affiliation: Department of Pharmacology, School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 2751, Australia ; Centre for Complementary Medicine Research, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 2751, Australia ; Molecular Medicine Research Group, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 2751, Australia.
authors.forename: Gerald
authors.initials: G
authors.lastname: Münch
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015850:Interleukin-6 / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; C528900:glial fibrillary astrocytic protein, mouse