PDF(Pubmed)
Abstract：
Tau is a microtubule-associated protein essential for microtubule assembly and stability in neurons. The abnormal intracellular accumulation of tau aggregates is a major characteristic of brains from patients with Alzheimer\'s disease (AD) and other tauopathies. In AD, the presence of neurofibrillary tangles (NFTs), which is composed of hyperphosphorylated tau protein, is positively correlated with the severity of the cognitive decline. Evidence suggests that the accumulation and aggregation of tau cause synaptic dysfunction and neuronal degeneration. Thus, the prevention of abnormal tau phosphorylation and elimination of tau aggregates have been proposed as therapeutic strategies for AD. However, currently tau-targeting therapies for AD and other tauopathies are limited. A number of dietary bioactive compounds have been found to modulate the posttranslational modifications of tau, including phosphorylation, small ubiquitin-like modifier (SUMO) mediated modification (SUMOylation) and acetylation, as well as inhibit tau aggregation and/or promote tau degradation. The advantages of using these dietary components over synthetic substances in AD prevention and intervention are their safety and accessibility. This review summarizes the mechanisms leading to tau pathology in AD and highlights the effects of bioactive compounds on the hyperphosphorylation, aggregation and clearance of tau protein. The potential of using these bioactive compounds for AD prevention and intervention is also discussed.
摘要：
Tau是一种微管相关蛋白，对于神经元中的微管组装和稳定性至关重要。tau聚集体的异常细胞内积累是阿尔茨海默病（AD）和其他tau蛋白病患者大脑的主要特征。在AD中,神经原纤维缠结（NFT）的存在，它由过度磷酸化的tau蛋白组成，与认知能力下降的严重程度呈正相关。证据表明tau的积累和聚集导致突触功能障碍和神经元变性。因此，已提出预防异常tau磷酸化和消除tau聚集体作为AD的治疗策略。然而,目前针对AD和其他tau蛋白病变的tau靶向治疗有限.已经发现许多膳食生物活性化合物可以调节tau的翻译后修饰，包括磷酸化，小泛素样修饰剂（SUMO）介导的修饰（SUMO化）和乙酰化，以及抑制tau聚集和/或促进tau降解。在AD预防和干预中使用这些膳食成分相对于合成物质的优点是它们的安全性和可及性。这篇综述总结了导致AD中tau病理的机制，并强调了生物活性化合物对过度磷酸化的影响。tau蛋白的聚集和清除。还讨论了使用这些生物活性化合物预防和干预AD的潜力。
