在一项新的研究中，来自美国国家卫生研究院的研究人员证实当把一种被称作TFP5的分子注射到患有阿尔茨海默病(Alzheimer's disease， AD)的模式小鼠体内时，它们的症状被逆转，它们的记忆也得到恢复，同时没有明显的毒副作用.相关研究结果发表在2013年1月那期FASEB Journal期刊上。
论文通信作者Harish C. Pant博士说，“根据对小鼠开展的TFP5治疗，我们希望在AD病人体内开展的临床试验应当能够延长他们的寿命和改善他们的生活质量.因此，我们认为TFP5应当是一种有效的治疗性化合物.”
为了作出这一发现，Pant和同事们利用患有AD的模式小鼠开展研究.一组小鼠被注射这种小分子TFP5，而另一组被注射生理盐水作为安慰剂.在进行一系列腹腔内注射TFP5之后，这组接受治疗的小鼠在多种疾病症状上表现出显着性下降，同时在视力上也得到恢复.此外，接受TFP5注射的小鼠并没有产生体重下降、神经焦虑或毒性症状.然而接受安慰剂注射的小鼠与期待中的那样发生病情恶化.TFP5是源自大脑中的一种关键性的被称作Cdk5的酶的调节分子.Cdk5过度激活参与斑块和神经元纤维缠结产生，其中斑块和神经元纤维缠结是AD的主要特征.
FASEB Journal期刊主编Gerald Weissmann博士说，“下一步就是证实这种分子在人们体内是否能够拥有相同的效果，如果没有的话，那么就去寻找哪些分子将拥有.鉴于我们知道我们能够靶向阿尔茨海默病中的基础性分子缺陷，因此我们希望能够找到比现在的治疗方法更好的和更加特异性的疗法.”(生物谷Bioon.com)
doi: 10.1096/fj.12-217497
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A truncated peptide from p35, a Cdk5 activator, prevents Alzheimer's disease phenotypes in model mice
Varsha Shukla*, Ya-Li Zheng§, Santosh K. Mishra‡, Niranjana D. Amin*, Joseph Steiner†, Philip Grant*, Sashi Kesavapany‖ and Harish C. Pant*,1
Alzheimer's disease (AD), one of the leading neurodegenerative disorders of older adults, which causes major socioeconomic burdens globally, lacks effective therapeutics without significant side effects. Besides the hallmark pathology of amyloid plaques and neurofibrillary tangles (NFTs), it has been reported that cyclin-dependent kinase 5 (Cdk5), a critical neuronal kinase, is hyperactivated in AD brains and is, in part, responsible for the above pathology. Here we show that a modified truncated 24-aa peptide (TFP5), derived from the Cdk5 activator p35, penetrates the blood-brain barrier after intraperitoneal injections, inhibits abnormal Cdk5 hyperactivity, and significantly rescues AD pathology (up to 70–80%) in 5XFAD AD model mice. The mutant mice, injected with TFP5 exhibit behavioral rescue, whereas no rescue was observed in mutant mice injected with either saline or scrambled peptide. However, TFP5 does not inhibit cell cycle Cdks or normal Cdk5/p35 activity, and thereby has no toxic side effects (even at 200 mg/kg), a common problem in most current therapeutics for AD. In addition, treated mice displayed decreased inflammation, amyloid plaques, NFTs, cell death, and an extended life by 2 mo. These results suggest TFP5 as a potential therapeutic, toxicity-free candidate for AD.—Shukla, V., Zheng, Y.-L., Mishra, S. K., Amin, N. D., Steiner, J., Grant, P., Kesavapany, S., Pant, H. C. A truncated peptide from p35, a Cdk5 activator, prevents Alzheimer's disease phenotypes in model mice.
