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Bcl-2 family-regulated apoptosis in health and disease

机译:Bcl-2家族调控健康与疾病中的细胞凋亡

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Abstract: Apoptotic cell death is essential for embryonic development, tissue homeostasis, and a well-functioning immune system, with aberrant apoptosis contributing to numerous disease conditions. Inadequate cell death is a major contributing factor to tumorigenesis, while excess cell death contributes to neurodegeneration and autoimmune disease. The major pathway of apoptotic cell death, the mitochondrial pathway, is controlled by the Bcl-2 family of proteins. The members of this family, more than 17 in humans, share significant sequence and structural homology, and fulfil either prosurvival or proapoptotic roles. Specific interactions between these functionally polar proteins, and their relative expression levels, govern the susceptibility of each cell to toxic insults. Here we review the current understanding on how apoptotic cell death is controlled by this important protein family. We also discuss how excessive or insufficient cell death can contribute to disease, and how targeting the Bcl-2 family offers novel therapeutic opportunities.
机译:摘要:凋亡细胞的死亡对于胚胎发育,组织稳态和免疫系统的正常运转至关重要,而异常的细胞凋亡导致许多疾病。细胞死亡不足是导致肿瘤发生的主要因素,而细胞死亡过多则导致神经退行性疾病和自身免疫性疾病。凋亡细胞死亡的主要途径,线粒体途径,是由Bcl-2家族蛋白控制的。该家族的成员,在人类中超过17个,具有重要的序列和结构同源性,并具有生存或凋亡作用。这些功能性极性蛋白之间的特异性相互作用及其相对表达水平决定着每个细胞对毒性侵害的敏感性。在这里,我们回顾了有关这一重要蛋白家族如何控制凋亡细胞死亡的当前理解。我们还讨论了过多或不足的细胞死亡如何导致疾病,以及靶向Bcl-2家族如何提供新的治疗机会。

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