Cilostazol, a phosphodiesterase 3 inhibitor, activates proteasome-mediated proteolysis and attenuates tauopathy and cognitive decline.
Cilostazol, a phosphodiesterase 3 inhibitor, activates proteasome-mediated proteolysis and attenuates tauopathy and cognitive decline.
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DOI：
10.1016/j.trsl.2017.11.004
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Myeku N
中科院分区：
文献类型：
--
作者：
Schaler AW;Myeku N
阿尔茨海默氏病和几种额颞变性，包括进行性上性麻痹和皮质型退化，其特征是将异常的tau蛋白累积到包括tau的大多数蛋白质中，包括大多数蛋白质。对蛋白酶体的功能进行注册可能会带来有害后果在本研究中，旨在清除异常tau的蛋白质稳态和疾病进展。眼磷酸/蛋白激酶A途径，衰减tauopathy和RTG4510小鼠的认知能力下降。
Alzheimer’s disease and several variants of frontotemporal degeneration including progressive supranuclear palsy and corticobasal degeneration are characterized by the accumulation of abnormal tau protein into aggregates. Most proteins, including tau, are degraded via the ubiquitin proteasome system, but when abnormal tau accumulates, the function of 26S proteasomes is downregulated. The negative effect of tau aggregates on the function of the proteasome can have deleterious consequences on protein homeostasis and disease progression. Developing therapies aimed at clearing abnormal tau are thus of considerable interest. In the present study, we investigated the effect of cilostazol, an FDA-approved selective phosphodiesterase 3 inhibitor, on a mouse model of tauopathy (line rTg4510). Administration of cilostazol for 30 days enhanced proteasome function via the cyclic adenosine 3',5'-monophosphate/protein kinase A pathway and attenuated tauopathy and cognitive decline in rTg4510 mice. These results suggest that cilostazol, or other FDA-approved drugs acting via the same pathway, has the potential to be repurposed for the treatment of patients with early-stage tauopathy.
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位点特异性蛋白酶体磷酸化控制细胞增殖和肿瘤发生。
影响因子：
21.3
作者：
Guo X;Wang X;Wang Z;Banerjee S;Yang J;Huang L;Dixon JE
通讯作者：
Dixon JE
DOI：
10.1523/jneurosci.4427-11.2012
发表时间：
2012-04-11
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Djakovic SN;Marquez-Lona EM;Jakawich SK;Wright R;Chu C;Sutton MA;Patrick GN
通讯作者：
Patrick GN
影响因子：
16.2
作者：
de Calignon A;Polydoro M;Suárez-Calvet M;William C;Adamowicz DH;Kopeikina KJ;Pitstick R;Sahara N;Ashe KH;Carlson GA;Spires-Jones TL;Hyman BT
通讯作者：
Hyman BT
影响因子：
15.9
作者：
Gong, B;Vitolo, OV;Arancio, O
通讯作者：
Arancio, O
影响因子：
4.8
作者：
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通讯作者：
Gonos, ES