|
KMID : 0613820110210050647
|
|
Journal of Life Science
2011 Volume.21 No. 5 p.647 ~ p.655
|
|
|
Phosphodiesterase Ⅲ Inhibitor Cilostazol Protects Amyloid β-Induced Neuronal Cell Injury via Peroxisome Proliferator-Activated Receptor-γ Activation
|
|
Park Sun-Haeng
Kim Ji-Hyun
Bae Sun-Sik
Hong Ki-Whan
Choi Byung-Tae
|
|
|
Abstract
|
|
|
|
The neurotoxicity of aggregated amyloid β (Aβ) has been implicated as a critical cause in the pathogenesis of Alzheimer’s disease (AD). It can cause neurotoxicity in AD by evoking a cascade of apoptosis to neuron. Here, we investigated the neuroprotective effects of cilostazol, which acts as a phosphodiesterase Ⅲ inhibitor, on Aβ25-35-induced cytotoxicity in mouse neuronal cells and cognitive decline in the C57BL/6J AD mouse model via peroxisome proliferator-activated receptor (PPAR)-γ activation. Aβ25-35 significantly reduced cell viability and increased the number of apoptotic-like cells. Cilostazol treatment recovered cells from Aβ-induced cell death as well as rosiglitazone, a PPAR-γ activator. These effects were suppressed by GW9662, an antagonist of PPAR-γ activity, indicative of a PPAR-γ -mediated signaling. In addition, cilostazol and rosiglitazone also restored PPAR-γ activity levels that had been altered as a result of Aβ25-35 treatment, which were antagonized by GW9662. Furthermore, cilostazol also markedly decreased the number of apoptotic-like cells and decreased the Bax/Bcl-2 ratio. Intracerebroventricular injection of Aβ25-35 in C57BL/6J mice resulted in impaired cognitive function. Oral administration of cilostazol (20 ㎎/㎏) for 2 weeks before Aβ25-35 injection and once a day for 4 weeks post-surgery almost completely prevented the Aβ25-35-induced cognitive deficits, as did rosiglitazone. Taken together, our findings suggest that cilostazol could attenuate Aβ25-35-induced neuronal cell injury and apoptosis as well as promote the survival of neuronal cells, subsequently improving cognitive decline in AD, partly because of PPAR-γ activation. The phosphodiesterase Ⅲ inhibitor cilostazol may be the basis of a novel strategy for the therapy of AD.
|
|
|
KEYWORD
|
|
|
Alzheimer’s disease, amyloid β, apoptosis, cell injury
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|