Unitat de Farmacologia i Farmacognòsia Facultat de Farmàcia, Institut de Biomedicina (IBUB), Centros de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Universitat de Barcelona, Barcelona, Spain.
J Neurochem. 2010 Sep 1;114(5):1315-22. doi: 10.1111/j.1471-4159.2010.06853.x. Epub 2010 Jun 8.
The MAPK family is formed by extracellular signal-regulated kinases p38 kinase and stress-activated protein kinases (SAPK/JNK). There are three genes that encode for three JNK proteins. JNK3 is mainly expressed in the central nervous system and has been related to various processes in that tissue. Specifically, JNK3 plays a crucial role in neuronal death in several neurodegenerative diseases. The activation of this kinase has been described in epilepsy, Alzheimer's disease, Parkinson's disease and Huntington's disease. Different studies have shown that the lack of the Jnk3 gene confers neuroprotection. However, the specific mechanism involved in such neuroprotection has not yet been elucidated. Therefore, in the present study, we analyzed the neuroprotection in mice lacking Jnk3 against neuronal death induced by kainic acid. Moreover, we analyzed the activation of different MAPKs. The results revealed that neuronal death was attenuated and different activation/inactivation of p38 and extracellular signal-regulated kinases 1/2 was reported with respect to control. Therefore, the data indicate that the lack of the JNK3 protein modulates other MAPKs and these changes could also have a pivotal role in neuroprotection.
MAPK 家族由细胞外信号调节激酶 p38 激酶和应激激活蛋白激酶（SAPK/JNK）组成。有三个基因编码三种 JNK 蛋白。JNK3 主要在中枢神经系统中表达，并与该组织中的各种过程有关。具体来说，JNK3 在几种神经退行性疾病中的神经元死亡中起着至关重要的作用。该激酶的激活已在癫痫、阿尔茨海默病、帕金森病和亨廷顿病中被描述。不同的研究表明，缺乏 Jnk3 基因赋予了神经保护作用。然而，这种神经保护所涉及的具体机制尚未阐明。因此，在本研究中，我们分析了缺乏 Jnk3 的小鼠对红藻氨酸诱导的神经元死亡的神经保护作用。此外，我们还分析了不同 MAPK 的激活情况。结果表明，与对照组相比，神经元死亡得到了减轻，并且 p38 和细胞外信号调节激酶 1/2 的不同激活/失活被报道。因此，数据表明 JNK3 蛋白的缺乏调节了其他 MAPK，这些变化在神经保护中也可能起着关键作用。
