c-Jun N-Terminal Kinase Inhibitors as Potential Leads for New Therapeutics for Alzheimer's Diseases.
c-Jun N-Terminal Kinase Inhibitors as Potential Leads for New Therapeutics for Alzheimer's Diseases.
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DOI：
10.3390/ijms21249677
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发表时间：
2020-12-18
影响因子：
5.6
通讯作者：
Laufer S
中科院分区：
文献类型：
--
作者：
Hepp Rehfeldt SC;Majolo F;Goettert MI;Laufer S
随着人们寿命的延长，阿尔茨海默病 (AD) 变得越来越普遍。对于60岁以上的人群，全球AD患病率估计为40.19%。关于该疾病引起的认知能力下降，丝裂原激活蛋白激酶（MAPK）途径，例如c-Jun氨基末端激酶（JNK）途径，与神经元和突触进行性丧失、脑萎缩和脑室增大有关，并被突触功能障碍、氧化应激和兴奋性毒性激活。如今，AD 症状是可以控制的，但疾病本身仍然无法治愈，因此考虑到 JNK 因其参与传播促凋亡信号而闻名，JNK3 的抑制已被探索作为可能的治疗靶点。本综述旨在介绍 JNK 的生物学方面，重点关注 JNK3 及其与 AD 的关系。由于一些药物/化合物在 III 期临床试验中失败，因此还探讨了最近可用于 AD 治疗的抑制剂的开发。本综述对 MAPK 家族的一般方面、治疗靶点和模型中的实验治疗进行了描述和讨论。
Alzheimer’s Disease (AD) is becoming more prevalent as the population lives longer. For individuals over 60 years of age, the prevalence of AD is estimated at 40.19% across the world. Regarding the cognitive decline caused by the disease, mitogen-activated protein kinases (MAPK) pathways such as the c-Jun N-terminal kinase (JNK) pathway are involved in the progressive loss of neurons and synapses, brain atrophy, and augmentation of the brain ventricles, being activated by synaptic dysfunction, oxidative stress, and excitotoxicity. Nowadays, AD symptoms are manageable, but the disease itself remains incurable, thus the inhibition of JNK3 has been explored as a possible therapeutic target, considering that JNK is best known for its involvement in propagating pro-apoptotic signals. This review aims to present biological aspects of JNK, focusing on JNK3 and how it relates to AD. It was also explored the recent development of inhibitors that could be used in AD treatment since several drugs/compounds in phase III clinical trials failed. General aspects of the MAPK family, therapeutic targets, and experimental treatment in models are described and discussed throughout this review.
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作者：
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通讯作者：
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