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阿尔茨海默病中的神经退行性变：淀粉样前体蛋白和早老素1细胞内信号传导的作用

Neurodegeneration in Alzheimer disease: role of amyloid precursor protein and presenilin 1 intracellular signaling.

作者信息

Nizzari Mario, Thellung Stefano, Corsaro Alessandro, Villa Valentina, Pagano Aldo, Porcile Carola, Russo Claudio, Florio Tullio

机构信息

Section of Pharmacology, Department of Internal Medicine and Center of Excellence for Biomedical Research, University of Genova, 16132 Genova, Italy.

出版信息

J Toxicol. 2012;2012:187297. doi: 10.1155/2012/187297. Epub 2012 Feb 8.

DOI:10.1155/2012/187297
PMID:22496686
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3306972/
Abstract

Alzheimer disease (AD) is a heterogeneous neurodegenerative disorder characterized by (1) progressive loss of synapses and neurons, (2) intracellular neurofibrillary tangles, composed of hyperphosphorylated Tau protein, and (3) amyloid plaques. Genetically, AD is linked to mutations in few proteins amyloid precursor protein (APP) and presenilin 1 and 2 (PS1 and PS2). The molecular mechanisms underlying neurodegeneration in AD as well as the physiological function of APP are not yet known. A recent theory has proposed that APP and PS1 modulate intracellular signals to induce cell-cycle abnormalities responsible for neuronal death and possibly amyloid deposition. This hypothesis is supported by the presence of a complex network of proteins, clearly involved in the regulation of signal transduction mechanisms that interact with both APP and PS1. In this review we discuss the significance of novel finding related to cell-signaling events modulated by APP and PS1 in the development of neurodegeneration.

摘要

阿尔茨海默病（AD）是一种异质性神经退行性疾病，其特征为：（1）突触和神经元进行性丧失；（2）由高度磷酸化的 Tau 蛋白组成的细胞内神经原纤维缠结；（3）淀粉样斑块。从遗传学角度来看，AD 与少数蛋白质即淀粉样前体蛋白（APP）以及早老素 1 和 2（PS1 和 PS2）的突变有关。AD 中神经退行性变的分子机制以及 APP 的生理功能尚不清楚。最近有一种理论提出，APP 和 PS1 调节细胞内信号以诱导导致神经元死亡并可能引发淀粉样沉积的细胞周期异常。这一假说得到了一个复杂蛋白质网络存在的支持，该网络显然参与了与 APP 和 PS1 相互作用的信号转导机制的调节。在这篇综述中，我们讨论了与 APP 和 PS1 调节的细胞信号事件相关的新发现对神经退行性变发展的意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaf9/3306972/007bc131782b/JT2012-187297.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaf9/3306972/0ed8615eb269/JT2012-187297.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaf9/3306972/28011296c0a5/JT2012-187297.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaf9/3306972/007bc131782b/JT2012-187297.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaf9/3306972/0ed8615eb269/JT2012-187297.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaf9/3306972/28011296c0a5/JT2012-187297.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaf9/3306972/007bc131782b/JT2012-187297.003.jpg

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