TY - JOUR
T1 - Ligand for translocator protein reverses pathology in a mouse model of Alzheimer's disease
AU - Barron, Anna M.
AU - Garcia-Segura, Luis M.
AU - Caruso, Donatella
AU - Jayaraman, Anusha
AU - Lee, Joo Won
AU - Melcangi, Roberto C.
AU - Pike, Christian J.
PY - 2013/5/15
Y1 - 2013/5/15
N2 - 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 nontransgenicmice.ThesefindingssuggestthatTSPOisapromisingtargetforthedevelopmentofpleiotropictreatmentstrategies for the management of AD.
AB - 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 nontransgenicmice.ThesefindingssuggestthatTSPOisapromisingtargetforthedevelopmentofpleiotropictreatmentstrategies for the management of AD.
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U2 - 10.1523/JNEUROSCI.1350-13.2013
DO - 10.1523/JNEUROSCI.1350-13.2013
M3 - Article
C2 - 23678130
AN - SCOPUS:84877753769
SN - 0270-6474
VL - 33
SP - 8891
EP - 8897
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 20
ER -