Tau aggregation and toxicity in tauopathic neurodegenerative diseases.
Tau aggregation and toxicity in tauopathic neurodegenerative diseases.
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DOI：
10.3233/jad-2008-14409
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发表时间：
2008-08
期刊：
影响因子：
--
通讯作者：
Kuret J
中科院分区：
文献类型：
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作者：
Honson NS;Kuret J
自从二十多年前发现tau蛋白作为阿尔茨海默病的神经系统病变的结构成分以来，tau蛋白已经涉及与神经变性相关的级联事件。具体来说，“tau假说”假定tau的功能失调，这是对未知刺激的反应，导致其细胞内组装成细丝，最终证明对产生它们的细胞有毒。tau假说得到了许多真实人类疾病病例的神经病理学和遗传学观察的支持。然而，旨在研究生物模型中的聚合物毒性的实验表明，一些聚合物物种可能是惰性的，或者可能具有神经保护功能。区分这些可能性的实验已经复杂的目前可用的生物模型，不完全概括疾病中看到的聚集条件。另外的模型系统，更好地接近生理条件下，可能有助于阐明聚集相关毒性的分子机制。在这里，我们研究了聚集和神经退行性变之间的联系，以及tau蛋白聚集介导的毒性问题的实验方法。
Since its discovery as a structural component of neurofibrillary lesions of Alzheimer's disease more than twenty years ago, tau protein has been implicated in the cascade of events associated with neurodegeneration. Specifically, the “tau hypothesis” posits that misfunction of tau, which occurs in response to unknown stimuli, results in its intracellular assembly into filaments that eventually prove toxic to the cells that produce them. The tau hypothesis is supported by numerous neuropathological and genetic observations of authentic human disease cases. However, experiments designed to study aggregate toxicity in biological models suggest that some aggregate species may be inert or could potentially serve a neuroprotective function. Distinguishing these possibilities experimentally has been complicated by currently available biological models, which do not fully recapitulate aggregation conditions seen in disease. Additional model systems which better approximate physiological conditions may help elucidate the molecular mechanisms involved in aggregation associated toxicity. Here we examine the accumulated evidence linking aggregation and neurodegeneration, and experimental approaches to the problem of tau aggregation-mediated toxicity.