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关于淀粉样前体蛋白功能的突触视角。

A synapse perspective on the function of the amyloid precursor protein.

作者信息

Kruse Pia, Eichler Amelie, Klukas Larissa, Lenz Maximilian

机构信息

Institute of Neuroanatomy and Cell Biology, Hannover Medical School, Hannover, Germany.

出版信息

Sci Prog. 2025 Jul-Sep;108(3):368504251360728. doi: 10.1177/00368504251360728. Epub 2025 Jul 30.

Abstract

The amyloid precursor protein (APP) is a transmembrane protein widely expressed throughout the brain, where it plays critical roles in both physiological and pathological states. APP undergoes complex post-translational processing by various secretases, a process that can lead to amyloid plaque formation via its amyloidogenic pathway. Consequently, APP has been extensively studied in the context of Alzheimer's disease (AD). However, emerging evidence highlights its physiological functions and the diverse roles of its cleavage fragments. This review explores the dual role of APP and its fragments, focusing on their contributions to synaptic structure, function, and plasticity. We summarize the mechanisms by which APP and its fragments influence synaptic dynamics and plasticity in the hippocampal CA1 region. These insights underline the importance of APP beyond amyloidogenesis, emphasizing its role in fundamental neurobiological processes and potential implications for understanding early AD-related synaptic dysfunction.

摘要

淀粉样前体蛋白(APP)是一种跨膜蛋白,在整个大脑中广泛表达,在生理和病理状态下均发挥关键作用。APP通过各种分泌酶进行复杂的翻译后加工,这一过程可通过其淀粉样生成途径导致淀粉样斑块形成。因此,在阿尔茨海默病(AD)的背景下,APP已得到广泛研究。然而,新出现的证据突出了其生理功能及其裂解片段的多种作用。本综述探讨了APP及其片段的双重作用,重点关注它们对突触结构、功能和可塑性的贡献。我们总结了APP及其片段影响海马CA1区突触动力学和可塑性的机制。这些见解强调了APP在淀粉样蛋白生成之外的重要性,突出了其在基本神经生物学过程中的作用以及对理解早期AD相关突触功能障碍的潜在意义。

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