Ischemic stroke is the leading cause of human disability and mortality in the world. The main problem in stroke therapy is the search of efficient neuroprotector capable to rescue neurons in the potentially salvageable transition zone (penumbra), which is expanding after brain damage. The data on molecular mechanisms of penumbra formation and expression of diverse signaling proteins in the penumbra during first 24 h after ischemic stroke are discussed. Two basic features of cell death regulation in the ischemic penumbra were observed: (1) both apoptotic and anti-apoptotic proteins are simultaneously over-expressed in the penumbra, so that the fate of individual cells is determined by the balance between these opposite tendencies. (2) Similtaneous and concerted up-regulation in the ischemic penumbra of proteins that execute apoptosis (caspases 3, 6, 7; Bcl-10, SMAC/DIABLO, AIF, PSR), signaling proteins that regulate different apoptosis pathways (p38, JNK, DYRK1A, neurotrophin receptor p75); transcription factors that control expression of various apoptosis regulation proteins (E2F1, p53, c-Myc, GADD153); and proteins, which are normally involved in diverse cellular functions, but stimulate apoptosis in specific situations (NMDAR2a, Par4, GAD65/67, caspase 11). Hence, diverse apoptosis initiation and regulation pathways are induced simultaneously in penumbra from very different initial positions. Similarly, various anti-apoptotic proteins (Bcl-x, p21/WAF-1, MDM2, p63, PKBα, ERK1, RAF1, ERK5, MAKAPK2, protein phosphatases 1α and MKP-1, estrogen and EGF receptors, calmodulin, CaMKII, CaMKIV) are upregulated. These data provide an integral view of neurodegeneration and neuroprotection in penumbra. Some discussed proteins may serve as potential targets for anti-stroke therapy.

中文翻译：

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缺血性中风后半影中的凋亡调节：前和抗凋亡蛋白的表达。

缺血性中风是世界上人类致残和死亡的主要原因。中风治疗的主要问题是寻找一种有效的神经保护剂，以挽救潜在可挽救的过渡区（半影）中的神经元，该过渡区在脑损伤后正在扩大。讨论了缺血性卒中后第一个24小时内半影形成和半影中各种信号蛋白表达的分子机制的数据。观察到缺血半影中细胞死亡调节的两个基本特征：（1）在半影中同时表达凋亡和抗凋亡蛋白，因此单个细胞的命运取决于这些相反趋势之间的平衡。（2）在缺血半影中，执行凋亡的蛋白质同时协调一致地上调（胱天蛋白酶3、6，7; Bcl-10，SMAC / DIABLO，AIF，PSR），调节不同凋亡途径的信号蛋白（p38，JNK，DYRK1A，神经营养蛋白受体p75）；转录因子，控制各种凋亡调节蛋白（E2F1，p53，c-Myc，GADD153）的表达；蛋白质和蛋白质，通常参与多种细胞功能，但在特定情况下会刺激细胞凋亡（NMDAR2a，Par4，GAD65 / 67，胱天蛋白酶11）。因此，从完全不同的初始位置在半影中同时诱导了不同的凋亡启动和调节途径。同样，各种抗凋亡蛋白（Bcl-x，p21 / WAF-1，MDM2，p63，PKBα，ERK1，RAF1，ERK5，MAKAPK2，蛋白磷酸酶1α和MKP-1，雌激素和EGF受体，钙调蛋白，CaMKII，CaMKIV ）上调。这些数据提供了半影神经变性和神经保护的完整视图。一些讨论过的蛋白质可能用作抗中风治疗的潜在靶标。