Endoplasmic reticulum stress and the unfolded protein response in disorders of myelinating glia.
Endoplasmic reticulum stress and the unfolded protein response in disorders of myelinating glia.
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DOI：
10.1016/j.brainres.2016.03.046
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发表时间：
2016-10-01
期刊：
影响因子：
2.9
通讯作者：
Popko, Brian
中科院分区：
文献类型：
--
作者：
Clayton, Benjamin L. L.;Popko, Brian
髓鞘对神经系统的正常功能至关重要。中枢神经系统中的少突胶质细胞和三叉神经节中的雪旺细胞是负责产生髓鞘的神经胶质细胞。髓鞘形成需要产生大量的蛋白质和富含脂质的膜，这给髓鞘胶质细胞的分泌途径带来了沉重的负担，使它们容易受到内质网(ER)的应激。细胞通过激活未折叠蛋白反应(UPR)来响应内质网应激。UPR最初是保护性的，但在长期未解决的应激情况下，UPR可导致应激细胞的凋亡性死亡。有强有力的证据表明，内质网应激和UPR在许多髓鞘和髓鞘胶质细胞疾病中发挥作用，包括多发性硬化症、Pelizaeus-Merzbacher病、消失性白质病和Charcot-Marie-Tooth病。在这篇综述中，我们讨论了内质网应激和UPR在这些髓鞘疾病中所起的作用。此外，我们还讨论了我们在了解UPR在这些疾病的小鼠模型中的遗传和药物操纵的影响方面取得的进展，以及这些研究支持的靶向UPR的新的治疗潜力。
Myelin is vital to the proper function of the nervous system. Oligodendrocytes in the CNS and Schwann cells in the PNS are the glial cells responsible for generating the myelin sheath. Myelination requires the production of a vast amount of proteins and lipid-rich membrane, which puts a heavy load on the secretory pathway of myelinating glia and leaves them susceptible to endoplasmic reticulum (ER) stress. Cells respond to ER stress by activating the unfolded protein response (UPR). The UPR is initially protective but in situations of prolonged unresolved stress the UPR can lead to the apoptotic death of the stressed cell. There is strong evidence that ER stress and the UPR play a role in a number of disorders of myelin and myelinating glia, including multiple sclerosis, Pelizaeus-Merzbacher disease, Vanishing White Matter Disease, and Charcot-Marie-Tooth disease. In this review we discuss the role that ER stress and the UPR play in these disorders of myelin. In addition, we discuss the progress that has been made in our understanding of the effect genetic and pharmacological manipulation of the UPR has in mouse models of these disorders and the novel therapeutic potential of targeting the UPR that these studies support.
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DOI：
10.1023/a:1007053411667
发表时间：
1999-04-01
期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
--
作者：
Ching, W;Zanazzi, G;Salzer, JL
通讯作者：
Salzer, JL
DOI：
10.1126/science.aaa4484
发表时间：
2015-04-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Das I;Krzyzosiak A;Schneider K;Wrabetz L;D'Antonio M;Barry N;Sigurdardottir A;Bertolotti A
通讯作者：
Bertolotti A
影响因子：
5.8
作者：
Cunnea, Paula;Mhaille, Aoife Ni;FitzGerald, Una
通讯作者：
FitzGerald, Una
影响因子：
64.8
作者：
Calfon, M;Zeng, HQ;Ron, D
通讯作者：
Ron, D
影响因子：
64.8
作者：
Fuenfschilling, Ursula;Supplie, Lotti M.;Mahad, Don;Boretius, Susann;Saab, Aiman S.;Edgar, Julia;Brinkmann, Bastian G.;Kassmann, Celia M.;Tzvetanova, Iva D.;Moebius, Wiebke;Diaz, Francisca;Meijer, Dies;Suter, Ueli;Hamprecht, Bernd;Sereda, Michael W.;Moraes, Carlos T.;Frahm, Jens;Goebbels, Sandra;Nave, Klaus-Armin
通讯作者：
Nave, Klaus-Armin