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阿尔茨海默病中内嗅皮质II对神经变性的易损性。

Vulnerability of the entorhinal cortex II to neurodegeneration in Alzheimer's disease.

作者信息

Reyes-Pablo Aldelmo Emmanuel, Luna-Viramontes Nabil Itzi, Montiel-Sosa José Francisco, Ontiveros-Torres Miguel Ángel, Garcés-Ramírez Linda, de la Cruz-López Fidel, Apátiga-Pérez Ricardo, Villanueva-Fierro Ignacio, Hernandes-Alejandro Mario, Jaramillo-Loranca Blanca Estela, Vargas-Hernández Genaro, Pacheco-Herrero Mar, Luna-Muñoz José

机构信息

National Dementia BioBank, AMPAEYDEN A.C., and Federación Mexicana de Alzheimer, Estado de México CP 54743, México.

Escuela Nacional de Ciencias Biológicas, Depto. de Fisiología, Instituto Politécnico Nacional, Ciudad de México CP 07700, México.

出版信息

Brain Commun. 2025 Feb 26;7(2):fcaf091. doi: 10.1093/braincomms/fcaf091. eCollection 2025.

Abstract

Alzheimer's disease is characterized by progressive memory loss and deterioration of cognitive functions. The presence of neurofibrillary tangles in the hippocampal areas (perforant pathway) correlates with cognitive impairment. Pathological processing of tau protein is characterized by post-translational changes such as hyperphosphorylation and truncation, which favour conformational changes within tau. These conformational changes can be regional (dependent on phosphorylation) or structural (depending on regional conformational changes and truncation). Through immunohistochemical and immunofluorescence staining in hippocampus Alzheimer disease brains and quantification in tissue stained with TG3 antibody and analysed by confocal microscopy, we have been able to demonstrate that TG3 correlates with cognitive impairment. In the process of tangle evolution, TG3 is present in pre-tangle. This epitope of the TG3 antibody was very stable to proteolytic processing by caspase-3; truncation is evidenced by the TauC-3 antibody. The entorhinal cortex showed high sensitivity to neurodegeneration and pathological tau processing.

摘要

阿尔茨海默病的特征是进行性记忆丧失和认知功能衰退。海马区(穿通通路)中神经原纤维缠结的存在与认知障碍相关。tau蛋白的病理加工特征为翻译后变化,如过度磷酸化和截短,这有利于tau蛋白内的构象变化。这些构象变化可以是区域性的(取决于磷酸化)或结构性的(取决于区域性构象变化和截短)。通过对阿尔茨海默病患者大脑海马区进行免疫组织化学和免疫荧光染色,并使用TG3抗体对染色组织进行定量分析,然后通过共聚焦显微镜进行分析,我们已经能够证明TG3与认知障碍相关。在缠结演变过程中,TG3存在于缠结前阶段。TG3抗体的这个表位对caspase-3的蛋白水解加工非常稳定;TauC-3抗体证实了截短的存在。内嗅皮质对神经退行性变和病理性tau加工表现出高度敏感性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b05/11897590/d23daa4fd9b4/fcaf091_ga.jpg

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