Collapsin Response Mediator Protein-2 (CRMP2) is a Plausible Etiological Factor and Potential Therapeutic Target in Alzheimer's Disease: Comparison and Contrast with Microtubule-Associated Protein Tau.
Collapsin Response Mediator Protein-2 (CRMP2) is a Plausible Etiological Factor and Potential Therapeutic Target in Alzheimer's Disease: Comparison and Contrast with Microtubule-Associated Protein Tau.
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DOI：
10.3233/jad-160076
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发表时间：
2016-04-15
期刊：
影响因子：
--
通讯作者：
Kursula P
中科院分区：
文献类型：
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作者：
Hensley K;Kursula P
阿尔茨海默病（AD）长期以来被认为是一种病理学，其必须由异常的淀粉样β蛋白前体（AβPP）加工、功能失调的tau蛋白加工或这两种因素的组合引起。这是一个合理的假设，因为淀粉样β肽（Aβ）蓄积和tau过度磷酸化是AD的定义性组织学特征，并且因为AβPP和tau突变可导致人类AD或动物模型中的AD样特征。尽管如此，其他蛋白质的球员正在出现，人们可以说是重要的病因球员在亚组的AD和潜在的新的，可药用的目标。特别是，微管相关蛋白CRMP 2（β-内酰胺酶反应介体蛋白-2）与tau蛋白具有惊人的相似性，并且与AD类似。与tau蛋白一样，CRMP 2动态调节微管稳定性;它受相同的激酶作用;在神经元缠结（NFT）中类似地收集;当被隔离在NFT中时，与关键的突触稳定因子复合。此外，CRMP 2被认为是一种重要的衔接蛋白，参与囊泡运输、淀粉样蛋白生成和自噬，而tau蛋白则不是。这篇综述系统地比较了CRMP 2与AD背景下tau蛋白的生物学特性，并探讨了CRMP 2是AD中一种病因学重要蛋白质并参与可合理参与治疗益处的途径的假设。
Alzheimer’s disease (AD) has long been viewed as a pathology that must be caused either by aberrant amyloid-β protein precursor (AβPP) processing, dysfunctional tau protein processing, or a combination of these two factors. This is a reasonable assumption because amyloid-β peptide (Aβ) accumulation and tau hyperphosphorylation are the defining histological features in AD, and because AβPP and tau mutations can cause AD in humans or AD-like features in animal models. Nonetheless, other protein players are emerging that one can argue are significant etiological players in subsets of AD and potentially novel, druggable targets. In particular, the microtubule-associated protein CRMP2 (collapsin response mediator protein-2) bears striking analogies to tau and is similarly relevant to AD. Like tau, CRMP2 dynamically regulates microtubule stability; it is acted upon by the same kinases; collects similarly in neurofibrillary tangles (NFTs); and when sequestered in NFTs, complexes with critical synapse-stabilizing factors. Additionally, CRMP2 is becoming recognized as an important adaptor protein involved in vesicle trafficking, amyloidogenesis and autophagy, in ways that tau is not. This review systematically compares the biology of CRMP2 to that of tau in the context of AD and explores the hypothesis that CRMP2 is an etiologically significant protein in AD and participates in pathways that can be rationally engaged for therapeutic benefit.