The NLRP3 inflammasome: a potential therapeutic target for traumatic brain injury.
The NLRP3 inflammasome: a potential therapeutic target for traumatic brain injury.
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NLRP 3炎性小体：创伤性脑损伤的潜在治疗靶点
DOI：
10.4103/1673-5374.286951
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发表时间：
2021-01
影响因子：
6.1
通讯作者：
Ishrat T
中科院分区：
文献类型：
--
作者：
Ismael S;Ahmed HA;Adris T;Parveen K;Thakor P;Ishrat T
虽然导致创伤性脑损伤后继发性脑损伤的确切机制是复杂和模糊的，但许多研究表明，炎症反应是创伤性脑损伤发病机制中明显和早期的特征。炎性小体是多蛋白复合物，其促进半胱天冬酶-1的刺激并随后诱导促炎细胞因子（例如白介素-1 β和白介素-18）的成熟和分泌。这些细胞因子在促进先天免疫应答和炎症中起关键作用。在各种炎性体复合物中，NOD样受体家族的含pyrin结构域3（NLRP 3）炎性体是最好的表征，NLRP 3在包括创伤性脑损伤在内的各种脑疾病中的关键作用已被证明。最近的几项研究揭示了NLRP 3炎性体在识别创伤性脑损伤后细胞损伤和刺激对无菌组织损伤的炎症反应中的贡献。更重要的是，阻断或抑制NLRP 3炎性体的活化可能具有在创伤性脑损伤期间挽救组织损伤的实质性潜力。在这篇综述中，我们总结了最近描述的机制，参与激活和调节的NLRP 3炎性小体。此外，我们回顾了最近的调查NLRP 3炎性小体在TBI的病理生理学的贡献，目前的进展和潜在的NLRP 3靶向治疗的挑战。NLRP 3炎性体激活对创伤性脑损伤的显著贡献意味着专注于靶向特定炎性体组分的治疗方法可以显著改善创伤性脑损伤的结果。
Although the precise mechanisms contributing to secondary brain injury following traumatic brain injury are complex and obscure, a number of studies have demonstrated that inflammatory responses are an obvious and early feature in the pathogenesis of traumatic brain injury. Inflammasomes are multiprotein complexes that prompt the stimulation of caspase-1 and subsequently induce the maturation and secretion of proinflammatory cytokines, such as interleukin-1β and interleukin-18. These cytokines play a pivotal role in facilitating innate immune responses and inflammation. Among various inflammasome complexes, the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is the best characterized, a crucial role for NLRP3 has been demonstrated in various brain diseases, including traumatic brain injury. Several recent studies have revealed the contribution of NLRP3 inflammasome in identifying cellular damage and stimulating inflammatory responses to aseptic tissue injury after traumatic brain injury. Even more important, blocking or inhibiting the activation of the NLRP3 inflammasome may have substantial potential to salvage tissue damage during traumatic brain injury. In this review, we summarize recently described mechanisms that are involved in the activation and regulation of the NLRP3 inflammasome. Moreover, we review the recent investigations on the contribution of the NLRP3 inflammasome in the pathophysiology of TBI, and current advances and challenges in potential NLRP3-targeted therapies. A significant contribution of NLRP3 inflammasome activation to traumatic brain injury implies that therapeutic approaches focused on targeting specific inflammasome components could significantly improve the traumatic brain injury outcomes.
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影响因子：
32.4
作者：
de Almeida L;Khare S;Misharin AV;Patel R;Ratsimandresy RA;Wallin MC;Perlman H;Greaves DR;Hoffman HM;Dorfleutner A;Stehlik C
通讯作者：
Stehlik C
影响因子：
4.7
作者：
Hanamsagar R;Torres V;Kielian T
通讯作者：
Kielian T
DOI：
10.1073/pnas.0611496104
发表时间：
2007-05-08
影响因子：
11.1
作者：
Duncan, Joseph A.;Bergstralht, Daniel T.;Ting, Jenny Pan-Yun
通讯作者：
Ting, Jenny Pan-Yun
影响因子：
64.5
作者：
Gurcel, Laure;Abrami, Laurence;van der Goot, F. Gisou
通讯作者：
van der Goot, F. Gisou
影响因子：
4.7
作者：
Bhowmick, Saurav;D'Mello, Veera;Abdul-Muneer, P. M.
通讯作者：
Abdul-Muneer, P. M.