The Proteostasis Network: A Global Therapeutic Target for Neuroprotection after Spinal Cord Injury.
The Proteostasis Network: A Global Therapeutic Target for Neuroprotection after Spinal Cord Injury.
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蛋白抑制网络：脊髓损伤后神经保护的全球治疗目标。
DOI：
10.3390/cells11213339
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发表时间：
2022-10-22
期刊：
影响因子：
6
通讯作者：
Hetman, Michal
中科院分区：
文献类型：
--
作者：
Whittemore, Scott R.;Saraswat Ohri, Sujata;Forston, Michael D.;Wei, George Z.;Hetman, Michal
关键词：
蛋白质稳态（蛋白质稳态）对细胞和生物体的生存至关重要。它受到多种保守途径的严格调控，包括泛素-蛋白酶体系统、自噬、热休克反应、整合应激反应和未折叠蛋白反应。这些重叠的蛋白质稳态维持模块响应于各种形式的细胞应激以及有机体损伤。虽然蛋白质稳态恢复和最终生物体存活是这种调节的主要进化驱动力，但蛋白质稳态的未解决的破坏可能会参与这些途径的促凋亡介质以消除缺陷细胞。在这篇综述中，我们讨论了蛋白稳态的创伤性脊髓损伤（SCI）的发病机制的贡献。大多数已发表的报告集中在SCI后急性/亚急性组织损伤中蛋白质稳态网络的作用。这些报告揭示了一个复杂的图片与细胞类型和/或蛋白质稳态介导剂的损失的神经元和/或神经胶质细胞，往往转化为相应的调制功能恢复的具体影响。目前，蛋白质稳态网络对神经修复、损伤后可塑性以及SCI的全身表现（包括免疫系统、代谢或心血管功能的失调）等现象的影响尚未得到充分研究。然而，由于靶向蛋白质稳态网络的潜在干预措施预计会影响SCI后受损的多个器官系统中的许多细胞类型，因此此类疗法可能会在广泛的高度可变的人类SCI中产生有益的效果。
Proteostasis (protein homeostasis) is critical for cellular as well as organismal survival. It is strictly regulated by multiple conserved pathways including the ubiquitin-proteasome system, autophagy, the heat shock response, the integrated stress response, and the unfolded protein response. These overlapping proteostasis maintenance modules respond to various forms of cellular stress as well as organismal injury. While proteostasis restoration and ultimately organism survival is the main evolutionary driver of such a regulation, unresolved disruption of proteostasis may engage pro-apoptotic mediators of those pathways to eliminate defective cells. In this review, we discuss proteostasis contributions to the pathogenesis of traumatic spinal cord injury (SCI). Most published reports focused on the role of proteostasis networks in acute/sub-acute tissue damage post-SCI. Those reports reveal a complex picture with cell type- and/or proteostasis mediator-specific effects on loss of neurons and/or glia that often translate into the corresponding modulation of functional recovery. Effects of proteostasis networks on such phenomena as neuro-repair, post-injury plasticity, as well as systemic manifestations of SCI including dysregulation of the immune system, metabolism or cardiovascular function are currently understudied. However, as potential interventions that target the proteostasis networks are expected to impact many cell types across multiple organ systems that are compromised after SCI, such therapies could produce beneficial effects across the wide spectrum of highly variable human SCI.
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影响因子：
12.7
作者：
Ahlgren, S;Li, GL;Olsson, Y
通讯作者：
Olsson, Y
影响因子：
3.7
作者：
Wei GZ;Saraswat Ohri S;Khattar NK;Listerman AW;Doyle CH;Andres KR;Karuppagounder SS;Ratan RR;Whittemore SR;Hetman M
通讯作者：
Hetman M
p62/SQSTM1形成自噬降解的蛋白质聚集体，并对亨廷顿蛋白诱导的细胞死亡具有保护作用。
影响因子：
7.8
作者：
Bjorkoy, Geir;Lamark, Trond;Brech, Andreas;Outzen, Heidi;Perander, Maria;Overvatn, Aud;Stenmark, Harald;Johansen, Terje
通讯作者：
Johansen, Terje
影响因子：
3.7
作者：
Bigford, Gregory E.;Bracchi-Ricard, Valerie C.;Bethea, John R.
通讯作者：
Bethea, John R.
影响因子：
6.2
作者：
Bankston, Andrew N.;Forston, Michael D.;Whittennore, Scott R.
通讯作者：
Whittennore, Scott R.