Targeting the 26S Proteasome To Protect Against Proteotoxic Diseases.
Targeting the 26S Proteasome To Protect Against Proteotoxic Diseases.
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DOI：
10.1016/j.molmed.2017.11.006
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发表时间：
2018-01
影响因子：
13.6
通讯作者：
Duff KE
中科院分区：
文献类型：
--
作者：
Myeku N;Duff KE
错误折叠蛋白的聚集体会损害26S蛋白酶体复合物的功能，使神经元容易受到加速和受损的蛋白质稳态，从而有助于神经变性的发病机理。旨在通过关键亚基表位的磷酸化增强26S蛋白酶体功能的策略在减少疾病小鼠模型中的蛋白质聚集体方面有效。我们讨论如何将磷酸二酯酶（PDE）抑制剂和G蛋白偶联受体（GPCR）靶向药物视为候选药物，该药物作用于第二降使者信号转导。候选者的范围可能会解决需要区域，细胞，细胞室特异性调制的需求。鉴于针对CAMP/CGMP信号传导的一系列临床和实验药物，我们建议将靶向次级信使的蛋白酶体激活剂被用作治疗或预防某些神经退行性疾病的新型药物。
Aggregates of misfolded proteins can compromise the function of the 26S proteasome complex, leaving neurons susceptible to accelerated and impaired protein homeostasis, thereby contributing to the pathogenesis of neurodegeneration. Strategies aimed at enhancing the function of the 26S proteasome via phosphorylation of key subunit epitopes have been effective in reducing protein aggregates in mouse models of disease. We discuss how phosphodiesterase (PDE) inhibitors and G protein-coupled receptor (GPCR)-targeted drugs might be considered as candidate therapeutics, acting on second messenger signal transduction. The range of candidates might address the need forregion-,cell-,oreven cellular compartment-specific modulation. Given the array of clinical and experimental drugs targeting cAMP/cGMP signaling, we propose that proteasome activators targeting secondary messengers might be exploited as novel agents for the treatment or prevention of some neurodegenerative diseases.
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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
DOI：
10.1046/j.1365-2990.2000.026002143.x
发表时间：
2000-04-01
影响因子：
5
作者：
Belichenko, PV;Brown, D;Fraser, JR
通讯作者：
Fraser, JR
影响因子：
48
作者：
Dieck, Susanne Tom;Kochen, Lisa;Hanus, Cyril;Heumueller, Maximilian;Bartnik, Ina;Nassim-Assir, Belquis;Merk, Katrin;Mosler, Thorsten;Garg, Sakshi;Bunse, Stefanie;Tirrell, David A.;Schuman, Erin M.
通讯作者：
Schuman, Erin M.
影响因子：
16.2
作者：
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通讯作者：
Hyman BT
影响因子：
2.3
作者：
Andre, Ralph;Tabrizi, Sarah J.
通讯作者：
Tabrizi, Sarah J.