Peroxisome proliferator-activated receptor γ (PPARγ): A master gatekeeper in CNS injury and repair.
Peroxisome proliferator-activated receptor γ (PPARγ): A master gatekeeper in CNS injury and repair.
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过氧化物酶体增殖物激活受体γ (PPARγ)：中枢神经系统损伤和修复的主要看门人
DOI：
10.1016/j.pneurobio.2017.10.002
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发表时间：
2018-04
影响因子：
6.7
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Cai W;Yang T;Liu H;Han L;Zhang K;Hu X;Zhang X;Yin KJ;Gao Y;Bennett MVL;Leak RK;Chen J
过氧化物酶体增殖物激活受体γ（过氧化物酶体增殖物激活受体γ，过氧化物酶体增殖物激活受体γ）是一种广泛表达的配体调节的转录因子，其控制参与炎症、氧化还原平衡、营养因子产生、胰岛素敏感性以及脂质和葡萄糖代谢的基因的表达。合成的PPARγ激动剂（例如噻唑烷二酮类）用于治疗II型糖尿病，并有可能通过减轻合并症的影响来限制发生脑损伤（如卒中）的风险。如果发生脑损伤，PPARγ作为细胞保护性应激反应的主要守门人，提高细胞存活和恢复稳态平衡的机会。在急性损伤阶段，PPARγ通过抑制NFκB通路减轻炎症并刺激Nrf 2/ARE轴中和氧化应激来直接限制组织损伤。在急性脑损伤的慢性期，受损细胞中的PPARγ活化在灰质和白色物质的修复、血脑屏障的保护、神经血管单元的重建、炎症的消退和长期功能恢复中达到高潮。因此，PPARγ处于细胞命运决定的顶点，并对急性损伤状况的慢性进展产生深远影响。在此，我们综述了PPARγ在中风和脑创伤中的治疗潜力，并强调了PPARγ在长期组织修复中的新作用。我们描述了它的结构和功能，并确定了它的目标基因。炎症、代谢、细胞命运（增殖/分化/成熟/存活）和许多其他过程的PPARγ调节也与其他神经系统疾病相关。因此，PPARγ是治疗许多进行性神经系统疾病的有吸引力的靶点。
Peroxisome proliferator-activated receptor γ (PPARγ) is a widely expressed ligand-modulated transcription factor that governs the expression of genes involved in inflammation, redox equilibrium, trophic factor production, insulin sensitivity, and the metabolism of lipids and glucose. Synthetic PPARγ agonists (e.g. thiazolidinediones) are used to treat Type II diabetes and have the potential to limit the risk of developing brain injuries, such as stroke, by mitigating the influence of comorbidities. If brain injury develops, PPARγ serves as a master gatekeeper of cytoprotective stress responses, improving the chances of cellular survival and recovery of homeostatic equilibrium. In the acute injury phase, PPARγ directly restricts tissue damage by inhibiting the NFκB pathway to mitigate inflammation and stimulating the Nrf2/ARE axis to neutralize oxidative stress. During the chronic phase of acute brain injuries, PPARγ activation in injured cells culminates in the repair of gray and white matter, preservation of the blood-brain barrier, reconstruction of the neurovascular unit, resolution of inflammation, and long-term functional recovery. Thus, PPARγ lies at the apex of cell fate decisions and exerts profound effects on the chronic progression of acute injury conditions. Here, we review the therapeutic potential of PPARγ in stroke and brain trauma and highlight the novel role of PPARγ in long-term tissue repair. We describe its structure and function and identify the genes that it targets. PPARγ regulation of inflammation, metabolism, cell fate (proliferation/differentiation/maturation/survival), and many other processes also has relevance to other neurological diseases. Therefore, PPARγ is an attractive target for therapies against a number of progressive neurological disorders.
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DOI：
10.1161/atvbaha.112.300962
发表时间：
2013-04-01
影响因子：
8.7
作者：
Auclair, Martine;Vigouroux, Corinne;Caron-Debarle, Martine
通讯作者：
Caron-Debarle, Martine
影响因子：
6.7
作者：
Bath, Philip M.;Appleton, Jason P.;Sprigg, Nikola
通讯作者：
Sprigg, Nikola
影响因子：
3.3
作者：
Bauer, S;Hay, M;Moyse, E
通讯作者：
Moyse, E
DOI：
10.1007/s003290050147
发表时间：
1999-09-01
期刊：
CRITICAL REVIEWS IN NEUROSURGERY
影响因子：
--
作者：
Asano, T
通讯作者：
Asano, T
影响因子：
82.9
作者：
通讯作者：
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