title: Oral administration of histone deacetylase inhibitor MS-275 ameliorates neuroinflammation and cerebral amyloidosis and improves behavior in a mouse model.
abstract: Alzheimer disease is the most common neurodegenerative disease and the major cause of dementia. In addition to β-amyloid aggregation and hyperphosphorylated tau, neuroinflammation also plays important roles in the pathophysiology of this multifactorial disorder. Histone deacetylase catalyzes deacetylation of histones and has important roles in the regulation of gene expression. Histone deacetylase inhibitors have been reported to exhibit neuroprotective and anti-neuroinflammatory activities and have therapeutic effects in several animal models of neurodegenerative diseases. Here, an efficient benzamide histone deacetylase inhibitor, MS-275, was orally administered by gavage to transgenic APP/PS1 mice, an animal model of cerebral amyloidosis for Alzheimer disease. After 10 days of treatment, MS-275 significantly ameliorated microglial activation and β-amyloid deposition in cerebral cortex and/or hippocampus. This was associated with improved nesting behavior, an important affiliative/social behavior. MS-275 also attenuated inflammatory activation of a mouse macrophage cell line in vitro. These results suggest that MS-275 may be a therapeutic option for Alzheimer disease and other neuroinflammatory diseases.
authors: Division of Immunopathology of the Nervous System, Institute of Pathology and Neuropathology, University of Tübingen, Tübingen, Germany. zhiyuan.zhang@medizin.uni-tuebingen.de
authors: Zhi-Yuan
authors: ZY
authors: Zhang
authors: Hermann J
authors: HJ
authors: Schluesener
mesh_terms: D000284:Administration, Oral; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000686:Amyloidosis / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001549:Benzamides / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage*; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011725:Pyridines / Q000008:administration & dosage*
chemical_list: D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D011725:Pyridines; C118739:entinostat