Istradefylline reduces memory deficits in aging mice with amyloid pathology
Adenosine A2A receptors are putative therapeutic targets for neurological disorders. The adenosine A2A receptor antagonist istradefylline is approved in Japan for Parkinson's disease and is being tested in clinical trials for this condition elsewhere. A2A receptors on neurons and astrocytes may...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-02-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996117302413 |
| _version_ | 1818675782790152192 |
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| author | Anna G. Orr Iris Lo Heike Schumacher Kaitlyn Ho Michael Gill Weikun Guo Daniel H. Kim Anthony Knox Takashi Saito Takaomi C. Saido Jeffrey Simms Carlee Toddes Xin Wang Gui-Qiu Yu Lennart Mucke |
| author_facet | Anna G. Orr Iris Lo Heike Schumacher Kaitlyn Ho Michael Gill Weikun Guo Daniel H. Kim Anthony Knox Takashi Saito Takaomi C. Saido Jeffrey Simms Carlee Toddes Xin Wang Gui-Qiu Yu Lennart Mucke |
| author_sort | Anna G. Orr |
| collection | DOAJ |
| description | Adenosine A2A receptors are putative therapeutic targets for neurological disorders. The adenosine A2A receptor antagonist istradefylline is approved in Japan for Parkinson's disease and is being tested in clinical trials for this condition elsewhere. A2A receptors on neurons and astrocytes may contribute to Alzheimer's disease (AD) by impairing memory. However, it is not known whether istradefylline enhances cognitive function in aging animals with AD-like amyloid plaque pathology. Here, we show that elevated levels of Aβ, C-terminal fragments of the amyloid precursor protein (APP), or amyloid plaques, but not overexpression of APP per se, increase astrocytic A2A receptor levels in the hippocampus and neocortex of aging mice. Moreover, in amyloid plaque-bearing mice, low-dose istradefylline treatment enhanced spatial memory and habituation, supporting the conclusion that, within a well-defined dose range, A2A receptor blockers might help counteract memory problems in patients with Alzheimer's disease. |
| first_indexed | 2024-12-17T08:33:03Z |
| format | Article |
| id | doaj.art-62158c22ffd34e74b78e39a026e12011 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T08:33:03Z |
| publishDate | 2018-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-62158c22ffd34e74b78e39a026e120112022-12-21T21:56:32ZengElsevierNeurobiology of Disease1095-953X2018-02-011102936Istradefylline reduces memory deficits in aging mice with amyloid pathologyAnna G. Orr0Iris Lo1Heike Schumacher2Kaitlyn Ho3Michael Gill4Weikun Guo5Daniel H. Kim6Anthony Knox7Takashi Saito8Takaomi C. Saido9Jeffrey Simms10Carlee Toddes11Xin Wang12Gui-Qiu Yu13Lennart Mucke14Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, CA 94158, USA; Correspondence to: A. Orr, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 413 East 69th Street, New York, NY 10021, USA.Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USAGladstone Institute of Neurological Disease, San Francisco, CA 94158, USAGladstone Institute of Neurological Disease, San Francisco, CA 94158, USAGladstone Institute of Neurological Disease, San Francisco, CA 94158, USAGladstone Institute of Neurological Disease, San Francisco, CA 94158, USAGladstone Institute of Neurological Disease, San Francisco, CA 94158, USAGladstone Institute of Neurological Disease, San Francisco, CA 94158, USALaboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako, Saitama 351-0198, JapanLaboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako, Saitama 351-0198, JapanGladstone Institute of Neurological Disease, San Francisco, CA 94158, USAGladstone Institute of Neurological Disease, San Francisco, CA 94158, USAGladstone Institute of Neurological Disease, San Francisco, CA 94158, USAGladstone Institute of Neurological Disease, San Francisco, CA 94158, USAGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, CA 94158, USA; Correspondence to: L. Mucke, Gladstone Institute of Neurological Disease, 1650 Owens Street, San Francisco, CA 94158, USA.Adenosine A2A receptors are putative therapeutic targets for neurological disorders. The adenosine A2A receptor antagonist istradefylline is approved in Japan for Parkinson's disease and is being tested in clinical trials for this condition elsewhere. A2A receptors on neurons and astrocytes may contribute to Alzheimer's disease (AD) by impairing memory. However, it is not known whether istradefylline enhances cognitive function in aging animals with AD-like amyloid plaque pathology. Here, we show that elevated levels of Aβ, C-terminal fragments of the amyloid precursor protein (APP), or amyloid plaques, but not overexpression of APP per se, increase astrocytic A2A receptor levels in the hippocampus and neocortex of aging mice. Moreover, in amyloid plaque-bearing mice, low-dose istradefylline treatment enhanced spatial memory and habituation, supporting the conclusion that, within a well-defined dose range, A2A receptor blockers might help counteract memory problems in patients with Alzheimer's disease.http://www.sciencedirect.com/science/article/pii/S0969996117302413Adenosine receptorsAlzheimer's diseaseAmyloid plaquesAntagonistAstrocytesBehavior |
| spellingShingle | Anna G. Orr Iris Lo Heike Schumacher Kaitlyn Ho Michael Gill Weikun Guo Daniel H. Kim Anthony Knox Takashi Saito Takaomi C. Saido Jeffrey Simms Carlee Toddes Xin Wang Gui-Qiu Yu Lennart Mucke Istradefylline reduces memory deficits in aging mice with amyloid pathology Neurobiology of Disease Adenosine receptors Alzheimer's disease Amyloid plaques Antagonist Astrocytes Behavior |
| title | Istradefylline reduces memory deficits in aging mice with amyloid pathology |
| title_full | Istradefylline reduces memory deficits in aging mice with amyloid pathology |
| title_fullStr | Istradefylline reduces memory deficits in aging mice with amyloid pathology |
| title_full_unstemmed | Istradefylline reduces memory deficits in aging mice with amyloid pathology |
| title_short | Istradefylline reduces memory deficits in aging mice with amyloid pathology |
| title_sort | istradefylline reduces memory deficits in aging mice with amyloid pathology |
| topic | Adenosine receptors Alzheimer's disease Amyloid plaques Antagonist Astrocytes Behavior |
| url | http://www.sciencedirect.com/science/article/pii/S0969996117302413 |
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