title: Minocycline attenuates Aβ oligomers-induced pro-inflammatory phenotype in primary microglia while enhancing Aβ fibrils phagocytosis.
abstract: Microglia, the brain innate immune cells, are activated in response to amyloid beta (Aβ) resulting in neuroinflammation in AD brains. Recently, two phenotypes have been described for microglia: the pro-inflammatory classical and the anti-inflammatory alternative. Changes in microglia phenotype that control their phagocytic function are yet to be determined. The highly neurotoxic Aβ oligomers (oAβ) formed at an early disease stage induce pro-inflammatory microglia activation releasing neurotoxic mediators and contributing to neurodegeneration. A novel strategy for AD treatment is to attenuate microglia-induced inflammation while maintaining efficient Aβ clearance. Minocycline effectively crosses the blood-brain barrier and has widely reported neuroprotective effects. Yet, its exact mechanism of neuroprotection and its effects on microglia are still unknown. The aim of this study is to investigate the effect of minocycline on the phagocytic uptake of fAβ by primary microglia in relation to their activation state in an inflammatory milieu generated by oAβ or LPS. The study shows that minocycline is able to attenuate oAβ-induced neuroinflammatory response of microglia by inhibiting their pro-inflammatory phenotype activation. In addition, a significant enhancement of fAβ phagocytosis by minocycline- treated microglia is reported for the first time, providing novel insight into its neuroprotective role in AD.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, The German University in Cairo, New Cairo City, Cairo, Egypt.
authors.forename: Ismail Amr
authors.initials: IA
authors.lastname: El-Shimy
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, The German University in Cairo, New Cairo City, Cairo, Egypt; Narcotics, Ergogenics & Poisons Department, National Research Center, Giza, Egypt.
authors.forename: Ola Ahmed
authors.initials: OA
authors.lastname: Heikal
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, The German University in Cairo, New Cairo City, Cairo, Egypt. Electronic address: nabila.hamdi@guc.edu.eg.
authors.forename: Nabila
authors.initials: N
authors.lastname: Hamdi
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D007249:Inflammation / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D008911:Minocycline / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D010587:Phagocytosis
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D008911:Minocycline
keywords: Alzheimer's disease; Amyloid beta fibrils; Amyloid beta oligomers; Microglia; Minocycline; Phagocytosis