Hyperphosphorylated tau (p-tau) and drug discovery in the context of Alzheimer's disease and related tauopathies.
Hyperphosphorylated tau (p-tau) and drug discovery in the context of Alzheimer's disease and related tauopathies.
复制标题
阿尔茨海默病和相关 tau 病背景下的过度磷酸化 tau (p-tau) 和药物发现。
DOI：
10.1016/j.drudis.2023.103487
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发表时间：
2023
影响因子：
7.4
通讯作者：
Fortin,JessicaS
中科院分区：
文献类型：
--
作者：
Moore,KendallBE;Hung,Ta-Jung;Fortin,JessicaS
重点痴呆涉及认知功能的慢性和进行性恶化。阿尔茨海默病是最常见的痴呆形式。异常过度磷酸化的tau（p-tau）与AD的发病机制有关。消除p-tau聚集可能导致神经元缠结（NFT）减少。阿尔茨海默病（AD）是最常见的痴呆形式，其特征在于细胞内神经纤维缠结（NFT）和细胞外β-淀粉样蛋白（βA）斑块。目前没有疾病修饰疗法可用于预防疾病的进展或治愈疾病。错误折叠的过度磷酸化tau（p-tau）被认为是AD和其他tau蛋白病发病机制中的关键点。令人信服的证据表明，它是NFT积累的关键驱动因素，并与AD患者的痴呆程度直接相关。因此，抑制tau蛋白过度磷酸化诱导的聚集可能是发现和开发AD患者治疗方法的可行策略。
HighlightsDementia involves the chronic and progressive deterioration of cognitive functions.Alzheimer’s disease is the most common form of dementia.Abnormally hyperphosphorylated tau (p-tau) is implicated in the pathogenesis of AD.Abrogating p-tau aggregation may lead to the reduction of neurofibrillary tangles (NFTs).Alzheimer’s disease (AD) is the most common form of dementia, characterized by intracellular neurofibrillary tangles (NFTs) and extracellular β-amyloid (βA) plaques. No disease-modifying therapy is currently available to prevent the progression of, or cure, the disease. Misfolded hyperphosphorylated tau (p-tau) is considered a pivotal point in the pathogenesis of AD and other tauopathies. Compelling evidence suggests that it is a key driver of the accumulation of NFTs and can be directly correlated with the extent of dementia in patients with AD. Therefore, inhibiting tau hyperphosphorylation-induced aggregation could be a viable strategy to discover and develop therapeutics for patients with AD.