Resnick Lynn, Fennell Myles
Wyeth Research, CN 8000, Princeton, NJ 08543-8000, USA.
Drug Discov Today. 2004 Nov 1;9(21):932-9. doi: 10.1016/S1359-6446(04)03251-9.
c-Jun N-terminal kinases (JNKs) have been recognized as important enzymes in cellular function. JNK3, which is predominantly found in CNS neurons, has been implicated in several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and stroke. In particular, JNK3 has been found to have an upstream role in neuronal ischemic apoptosis. JNK3 is highly expressed and activated in postmortem brains of individuals that suffered from Alzheimer's disease. Furthermore, mice that are deficient in JNK3 are more resistant to 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine (a neurotoxin that mimics the neuropathological characteristics of Parkinson's disease) than their wild-type littermates. Because of the involvement of JNK3 in neuronal diseases, the inhibition of this enzyme is an attractive therapeutic target.
c-Jun氨基末端激酶（JNKs）已被公认为细胞功能中的重要酶。JNK3主要存在于中枢神经系统神经元中，与多种神经退行性疾病有关，包括阿尔茨海默病、帕金森病和中风。特别是，已发现JNK3在神经元缺血性凋亡中起上游作用。JNK3在患有阿尔茨海默病的个体的死后大脑中高度表达并被激活。此外，JNK3缺陷的小鼠比其野生型同窝小鼠对1-甲基-4-苯基-1,2,4,6-四氢吡啶（一种模拟帕金森病神经病理学特征的神经毒素）更具抗性。由于JNK3参与神经元疾病，抑制这种酶是一个有吸引力的治疗靶点。
