Current Understanding of Neurodegenerative Diseases Associated With the Protein Tau.
Current Understanding of Neurodegenerative Diseases Associated With the Protein Tau.
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DOI：
10.1016/j.mayocp.2017.04.016
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发表时间：
2017-08
影响因子：
8.9
通讯作者：
Josephs KA
中科院分区：
文献类型：
--
作者：
Josephs KA
原发性 tau 蛋白病是一组神经退行性疾病，其中 tau 蛋白被认为是神经退行性过程的主要促成因素。在原发性 tau 蛋白病中，由于 tau 蛋白过度磷酸化，tau 蛋白（一种微管相关蛋白）与微管之间存在解离。 tau 蛋白和微管之间的这种解离导致 tau 蛋白原纤维化和包涵体形成以及微管功能障碍。不同的原发性tau蛋白病有不同的临床综合征，并且一些临床综合征可能与多种原发性tau蛋白病相关。因此，虽然一些临床综合征具有高度特异性，几乎可以诊断原发性 tau 病，但许多临床综合征则不然，因此很难诊断原发性 tau 病。最近，已经开发出与 tau 结合并可与正电子发射断层扫描相结合来检测生前纤维性 tau 的放射性配体，尽管初步数据表明这些配体在检测与许多原发性 tau 病相关的 tau 时可能不是非常敏感。该领域最近的另一个进展是有证据表明 tau 蛋白可能表现出与朊病毒相似的特性，尽管感染性传播尚未得到证实。已经有一些针对 tau 蛋白和微管功能障碍的临床试验，尽管没有任何疾病缓解作用。了解 tau 生物学对于开发可能对原发性 tau 病具有疾病缓解作用的药物至关重要。
The primary tauopathies are a group of neurodegenerative diseases in which tau is believed to be the major contributing factor of the neurodegenerative process. In the primary tauopathies, there is a disassociation between tau, a microtubule associated protein, and microtubules, as a result of tau hyperphosphorylation. This disassociation between tau and microtubules results in tau fibrillization and inclusion formation, and microtubule dysfunction. There are different clinical syndromes associated with different primary tauopathies, and some clinical syndromes can be associated with multiple primary tauopathies. Hence, while some clinical syndromes are highly specific and almost diagnostic of a primary tauopathy, many are not, making it difficult to diagnose a primary tauopathy. Recently, radioligands that bind to tau and can be combined with positron emission tomography to detect fibrillary tau antemortem have been developed, although preliminary data suggest that these ligands may not be very sensitive in detecting tau associated with many of the primary tauopathies. Another recent advancement in the field is evidence demonstrating that tau may show similar properties to prions although infective transmission has not been demonstrated. There have been a few clinical trials targeting tau and microtubule dysfunction, although none have had any disease modifying effects. Understanding tau biology is critical to the development of pharmacologic agents that could have disease modifying effects on the primary tauopathies.
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影响因子：
34.7
作者：
Frost, Bess;Diamond, Marc I.
通讯作者：
Diamond, Marc I.
影响因子：
48
作者：
Boxer, Adam L.;Lang, Anthony E.;Grossman, Murray;Knopman, David S.;Miller, Bruce L.;Schneider, Lon S.;Doody, Rachelle S.;Lees, Andrew;Golbe, Lawrence I.;Williams, David R.;Corvol, Jean-Cristophe;Ludolph, Albert;Burn, David;Lorenzl, Stefan;Litvan, Irene;Roberson, Erik D.;Hoeglinger, Guenter U.;Koestler, Mary;Jack, Clifford R., Jr.;Van Deerlin, Viviana;Randolph, Christopher;Lobach, Iryna V.;Heuer, Hilary W.;Gozes, Illana;Parker, Lesley;Whitaker, Steve;Hirman, Joe;Stewart, Alistair J.;Gold, Michael;Morimoto, Bruce H.
通讯作者：
Morimoto, Bruce H.
DOI：
10.1073/pnas.85.11.4051
发表时间：
1988-06-01
影响因子：
11.1
作者：
GOEDERT, M;WISCHIK, CM;KLUG, A
通讯作者：
KLUG, A
影响因子：
16.2
作者：
GOEDERT, M;SPILLANTINI, MG;CROWTHER, RA
通讯作者：
CROWTHER, RA
影响因子：
3.5
作者：
Baker, M;Litvan, I;Hutton, M
通讯作者：
Hutton, M