Luna-Viramontes Nabil Itzi, Campa-Córdoba B Berenice, Ontiveros-Torres Miguel Ángel, Harrington Charles R, Villanueva-Fierro Ignacio, Guadarrama-Ortíz Parménides, Garcés-Ramírez Linda, de la Cruz Fidel, Hernandes-Alejandro Mario, Martínez-Robles Sandra, González-Ballesteros Erik, Pacheco-Herrero Mar, Luna-Muñoz José
National Dementia BioBank, Departamento de Ciencias Biológicas, Facultad de Estudios Superiores, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Departamento de Fisiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico.
Front Cell Neurosci. 2020 Sep 10;14:247. doi: 10.3389/fncel.2020.00247. eCollection 2020.
Worldwide, around 50 million people have dementia. Alzheimer's disease (AD) is the most common type of dementia and one of the major causes of disability and dependency among the elderly worldwide. Clinically, AD is characterized by impaired memory accompanied by other deficiencies in the cognitive domain. Neuritic plaques (NPs) and neurofibrillary tangles (NFTs) are histopathological lesions that define brains with AD. NFTs consist of abundant intracellular paired helical filaments (PHFs) whose main constituent is tau protein. Tau undergoes posttranslational changes including hyperphosphorylation and truncation, both of which favor conformational changes in the protein. The sequential pathological processing of tau is illustrated with the following specific markers: pT231, TG3, AT8, AT100, and Alz50. Two proteolysis sites for tau have been described-truncation at glutamate 391 and at aspartate 421-and which can be demonstrated by reactivity with the antibodies 423 and TauC-3, respectively. In this review, we describe the molecular changes in tau protein as pre-NFTs progress to extracellular NFTs and during which the formation of a minimal nucleus of the filament, as the PHF core, occurs. We also analyzed the PHF core as the initiator of PHFs and tau phosphorylation as a protective neuronal mechanism against the assembly of the PHF core.
在全球范围内，约有5000万人患有痴呆症。阿尔茨海默病（AD）是最常见的痴呆类型，也是全球老年人残疾和依赖的主要原因之一。临床上，AD的特征是记忆力受损，并伴有认知领域的其他缺陷。神经炎性斑块（NPs）和神经原纤维缠结（NFTs）是定义AD大脑的组织病理学病变。NFTs由丰富的细胞内双螺旋丝（PHFs）组成，其主要成分是tau蛋白。Tau会发生翻译后变化，包括过度磷酸化和截断，这两者都有利于蛋白质的构象变化。tau的连续病理过程用以下特定标志物说明：pT231、TG3、AT8、AT100和Alz50。已经描述了tau的两个蛋白水解位点——谷氨酸391和天冬氨酸421处的截断——分别可以通过与抗体423和TauC-3的反应性来证明。在这篇综述中，我们描述了tau蛋白从预NFTs发展为细胞外NFTs过程中的分子变化，在此期间，作为PHF核心的细丝最小核形成。我们还分析了作为PHFs起始物的PHF核心以及作为针对PHF核心组装的保护性神经元机制的tau磷酸化。
