Josephs Keith A
Department of Neurology, Mayo Clinic, Rochester, MN.
Mayo Clin Proc. 2017 Aug;92(8):1291-1303. doi: 10.1016/j.mayocp.2017.04.016.
Primary tauopathies are a group of neurodegenerative diseases in which tau is believed to be the major contributing factor of the neurodegenerative process. In 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 as well as in microtubule dysfunction. There are different clinical syndromes associated with different primary tauopathies, and some clinical syndromes can be associated with multiple primary tauopathies. Hence, although 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 sensitive in detecting tau associated with many primary tauopathies. Another recent advancement in the field is evidence suggesting that tau may exhibit properties similar to those of prions, although infective transmission has not been shown. 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 pharmacological agents that could have disease-modifying effects on primary tauopathies.
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）与微管之间会发生解离。tau蛋白与微管之间的这种解离会导致tau蛋白纤维化和包涵体形成，以及微管功能障碍。不同的原发性tau蛋白病会有不同的临床综合征，而且一些临床综合征可能与多种原发性tau蛋白病相关。因此，尽管一些临床综合征具有高度特异性，几乎可以诊断原发性tau蛋白病，但许多并非如此，这使得原发性tau蛋白病的诊断变得困难。最近，已经开发出了与tau蛋白结合并可与正电子发射断层扫描相结合以在生前检测纤维状tau蛋白的放射性配体，不过初步数据表明，这些配体在检测与许多原发性tau蛋白病相关的tau蛋白时可能并不敏感。该领域的另一项最新进展是有证据表明tau蛋白可能具有与朊病毒相似的特性，尽管尚未显示出感染性传播。已经有一些针对tau蛋白和微管功能障碍的临床试验，不过尚无任何具有疾病修饰作用的药物。了解tau蛋白生物学对于开发可能对原发性tau蛋白病具有疾病修饰作用的药物至关重要。
