Transthyretin and the brain re-visited: is neuronal synthesis of transthyretin protective in Alzheimer's disease?
Transthyretin and the brain re-visited: is neuronal synthesis of transthyretin protective in Alzheimer's disease?
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DOI：
10.1186/1750-1326-6-79
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发表时间：
2011-11-23
影响因子：
15.1
通讯作者：
Buxbaum JN
中科院分区：
文献类型：
--
作者：
Li X;Buxbaum JN
自20世纪90年代中期以来，来自分散的独立实验室的少量出版物提供了数据，表明系统性淀粉样蛋白前体甲状腺素运载蛋白（TTR）可以与阿尔茨海默病（AD）的淀粉样蛋白生成β-淀粉样蛋白（Aβ）肽相互作用。一种淀粉样蛋白前体实际上可以抑制另一种淀粉样蛋白纤维形成的想法似乎很牵强。此外，似乎清楚的是，在CNS内，TTR仅在脉络丛上皮细胞中产生，而不在神经元中产生。最热情的作者宣称TTR在体内隔离Aβ，导致AD患者脑脊液（CSF）中TTR水平降低，并且这种关系是有益的。更谨慎的研究者仅仅展示了这两种分子之间的体外相互作用。在秀丽隐杆线虫中进行的一项体内研究表明，野生型人TTR可以抑制Aβ在蠕虫肌肉细胞中表达时观察到的异常。随后在人Aβ转基因小鼠中的研究，包括我们实验室的研究，也表明这种相互作用减少了Aβ沉积表型。我们已经回顾了分析这种关系的文献，包括最近的数据，研究可能解释这种影响的潜在机制。我们提出了一个模型，这是与大多数已发表的数据和目前的概念，AD发病机制，并可以作为一个假设，可以进行测试。
Since the mid-1990's a trickle of publications from scattered independent laboratories have presented data suggesting that the systemic amyloid precursor transthyretin (TTR) could interact with the amyloidogenic β-amyloid (Aβ) peptide of Alzheimer's disease (AD). The notion that one amyloid precursor could actually inhibit amyloid fibril formation by another seemed quite far-fetched. Further it seemed clear that within the CNS, TTR was only produced in choroid plexus epithelial cells, not in neurons. The most enthusiastic of the authors proclaimed that TTR sequestered Aβ in vivo resulting in a lowered TTR level in the cerebrospinal fluid (CSF) of AD patients and that the relationship was salutary. More circumspect investigators merely showed in vitro interaction between the two molecules. A single in vivo study in Caenorhabditis elegans suggested that wild type human TTR could suppress the abnormalities seen when Aβ was expressed in the muscle cells of the worm. Subsequent studies in human Aβ transgenic mice, including those from our laboratory, also suggested that the interaction reduced the Aβ deposition phenotype. We have reviewed the literature analyzing the relationship including recent data examining potential mechanisms that could explain the effect. We have proposed a model which is consistent with most of the published data and current notions of AD pathogenesis and can serve as a hypothesis which can be tested.
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影响因子：
3.9
作者：
Augustin, Sabine;Rimbach, Gerald;Cermak, Rainer
通讯作者：
Cermak, Rainer
DOI：
10.1016/s0140-6736(20)32205-4
发表时间：
2021-04-24
期刊：
Lancet (London, England)
影响因子：
--
作者：
Scheltens P;De Strooper B;Kivipelto M;Holstege H;Chételat G;Teunissen CE;Cummings J;van der Flier WM
通讯作者：
van der Flier WM
影响因子：
4.8
作者：
Buxbaum, JD;Liu, KN;Black, RA
通讯作者：
Black, RA
影响因子：
4.8
作者：
Cao, XW;Südhof, TC
通讯作者：
Südhof, TC
影响因子：
56.9
作者：
Cao, XW;Südhof, TC
通讯作者：
Südhof, TC