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Brief Communications

Ligand for Translocator Protein Reverses Pathology in a Mouse Model of Alzheimer's Disease

Anna M. Barron, Luis M. Garcia-Segura, Donatella Caruso, Anusha Jayaraman, Joo-Won Lee, Roberto C. Melcangi and Christian J. Pike
Journal of Neuroscience 15 May 2013, 33 (20) 8891-8897; DOI: https://doi.org/10.1523/JNEUROSCI.1350-13.2013
Anna M. Barron
1Davis School of Gerontology, University of Southern California, Los Angeles, California 90089,
2Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan,
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Luis M. Garcia-Segura
3Instituto Cajal, CSIC, E-28002 Madrid, Spain, and
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Donatella Caruso
4Department of Pharmacological and Biomolecular Sciences, Center of Excellence on Neurodegenerative Diseases, University of Milan, 20133 Milan, Italy
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Anusha Jayaraman
1Davis School of Gerontology, University of Southern California, Los Angeles, California 90089,
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Joo-Won Lee
1Davis School of Gerontology, University of Southern California, Los Angeles, California 90089,
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Roberto C. Melcangi
4Department of Pharmacological and Biomolecular Sciences, Center of Excellence on Neurodegenerative Diseases, University of Milan, 20133 Milan, Italy
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Christian J. Pike
1Davis School of Gerontology, University of Southern California, Los Angeles, California 90089,
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Abstract

Ligands of the translocator protein (TSPO) elicit pleiotropic neuroprotective effects that represent emerging treatment strategies for several neurodegenerative conditions. To investigate the potential of TSPO as a therapeutic target for Alzheimer's disease (AD), the current study assessed the effects of the TSPO ligand Ro5-4864 on the development of neuropathology in 3xTgAD mice. The effects of the TSPO ligand on neurosteroidogenesis and AD-related neuropathology, including β-amyloid accumulation, gliosis, and behavioral impairment, were examined under both early intervention (7-month-old young-adult male mice with low pathology) and treatment (24-month-old, aged male mice with advanced neuropathology) conditions. Ro5-4864 treatment not only effectively attenuated development of neuropathology and behavioral impairment in young-adult mice but also reversed these indices in aged 3xTgAD mice. Reduced levels of soluble β-amyloid were also observed by the combination of TSPO ligands Ro5-4864 and PK11195 in nontransgenic mice. These findings suggest that TSPO is a promising target for the development of pleiotropic treatment strategies for the management of AD.

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The Journal of Neuroscience: 33 (20)
Journal of Neuroscience
Vol. 33, Issue 20
15 May 2013
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Ligand for Translocator Protein Reverses Pathology in a Mouse Model of Alzheimer's Disease
Anna M. Barron, Luis M. Garcia-Segura, Donatella Caruso, Anusha Jayaraman, Joo-Won Lee, Roberto C. Melcangi, Christian J. Pike
Journal of Neuroscience 15 May 2013, 33 (20) 8891-8897; DOI: 10.1523/JNEUROSCI.1350-13.2013

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Ligand for Translocator Protein Reverses Pathology in a Mouse Model of Alzheimer's Disease
Anna M. Barron, Luis M. Garcia-Segura, Donatella Caruso, Anusha Jayaraman, Joo-Won Lee, Roberto C. Melcangi, Christian J. Pike
Journal of Neuroscience 15 May 2013, 33 (20) 8891-8897; DOI: 10.1523/JNEUROSCI.1350-13.2013
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