Tau-based therapeutic approaches for Alzheimer's disease - a mini-review.
Tau-based therapeutic approaches for Alzheimer's disease - a mini-review.
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DOI：
10.1159/000358875
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发表时间：
2014
期刊：
影响因子：
3.5
通讯作者：
Wisniewski T
中科院分区：
文献类型：
--
作者：
Boutajangout A;Wisniewski T
聚集的、过度磷酸化的tau蛋白作为神经元缠结（NFT）和神经元丝（NT）的积累是阿尔茨海默病（AD）的主要特征。在AD中发现的其他病变包括淀粉样斑块和嗜中性淀粉样血管病，两者都与淀粉样β（Aβ）肽的细胞外积累有关。AD是全球痴呆症最常见的原因。目前还没有有效的方法来治疗AD，甚至减缓它。AD病因的主导理论是淀粉样蛋白级联假说，其表明Aβ作为寡聚体和淀粉样蛋白斑块的聚集是AD发病机制的核心。已经开发了许多针对Aβ相关病理学的疗法，特别是各种免疫疗法。到目前为止，所有这些都在临床试验中失败了。最近，人们更加关注针对tau相关病理学的治疗，与淀粉样蛋白负荷相比，tau相关病理学与患者的认知状态相关性更好。tau病理学的免疫靶向已经显示出治疗AD小鼠模型中的tau病理学的巨大潜力。一些研究表明，被动和主动免疫接种都有效果。本文综述了近年来以病理性tau蛋白为靶点的治疗方法的研究进展，特别是免疫治疗方法的研究进展。
The accumulation of aggregated, hyperphosphorylated tau as neurofibrillary tangles (NFTs) and neuropil threads (NT) are cardinal features of Alzheimer’s disease (AD). The other lesions found in AD include amyloid plaques and congophilic amyloid angiopathy, both associated with the extracellular accumulation of the amyloid β (Aβ) peptide. AD is the most common cause of dementia globally. Currently there are no effective means to treat AD or even to slow it down. The dominant theory for the causation of AD is the amyloid cascade hypothesis, which suggests that the aggregation of Aβ as oligomers and amyloid plaques is central to the pathogenesis of AD. Numerous therapies have been developed directed to Aβ relate pathology, in particular various immunotherapeutic approaches. So far all of these have failed in clinical trials. Recently there has been more focus on therapy directed to tau related pathology, which correlates better with the cognitive status of patients, compared to the amyloid burden. Immunotherapeutic targeting of tau pathology has showed great potential to treat tau pathologies in mouse models of AD. A number of studies have shown the efficacy of both passive and active immunization. This review summarizes recent advances on therapy targeting pathological tau protein, in particular focusing on immunotherapeutic approaches which are showing great promise.
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影响因子：
4
作者：
del Ser, Teodoro;Steinwachs, Klaus C.;Leon, Teresa
通讯作者：
Leon, Teresa
影响因子：
3.7
作者：
d'Abramo C;Acker CM;Jimenez HT;Davies P
通讯作者：
Davies P
DOI：
10.1097/nen.0b013e31825018f7
发表时间：
2012-05
影响因子：
3.2
作者：
Nelson PT;Alafuzoff I;Bigio EH;Bouras C;Braak H;Cairns NJ;Castellani RJ;Crain BJ;Davies P;Del Tredici K;Duyckaerts C;Frosch MP;Haroutunian V;Hof PR;Hulette CM;Hyman BT;Iwatsubo T;Jellinger KA;Jicha GA;Kövari E;Kukull WA;Leverenz JB;Love S;Mackenzie IR;Mann DM;Masliah E;McKee AC;Montine TJ;Morris JC;Schneider JA;Sonnen JA;Thal DR;Trojanowski JQ;Troncoso JC;Wisniewski T;Woltjer RL;Beach TG
通讯作者：
Beach TG
DOI：
10.1073/pnas.93.20.11213
发表时间：
1996-10-01
影响因子：
11.1
作者：
Wischik, CM;Edwards, PC;Harrington, CR
通讯作者：
Harrington, CR
影响因子：
5.3
作者：
Hampel, Harald;Ewers, Michael;Basun, Hans
通讯作者：
Basun, Hans