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利用黑腹果蝇探索APPL在代谢和记忆中的多方面功能。

Exploring the multifaceted functions of APPL in metabolism and memory using Drosophila melanogaster.

作者信息

Nath Dharmendra Kumar, Lee Youngseok

机构信息

Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 02707, Republic of Korea.

Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 02707, Republic of Korea.

出版信息

Mol Cells. 2025 Jan;48(1):100163. doi: 10.1016/j.mocell.2024.100163. Epub 2024 Nov 26.

Abstract

Amyloid precursor protein (APP) is a single-pass transmembrane protein abundantly expressed in the central nervous system and implicated in familial Alzheimer's disease, a progressive neurodegenerative disorder that impairs memory. Here, we investigated the role of amyloid precursor protein-like (APPL) using the model organism Drosophila melanogaster. In this study, Appl null mutants exhibited a reduced lifespan under normal conditions and increased triglyceride levels, which were mitigated by metformin treatment. Additionally, taste-associative memory impairment in Appl mutants suggested APPL's role in memory formation, which was restored by curcumin supplementation. The Appl mutants also displayed reduced climbing ability, which was improved by supplementation with vitamins C (ascorbic acid) and B (riboflavin). These findings suggest that APPL is involved in metabolic regulation, cognition, climbing activity, and aging in Drosophila melanogaster.

摘要

淀粉样前体蛋白(APP)是一种单次跨膜蛋白,在中枢神经系统中大量表达,并与家族性阿尔茨海默病有关,这是一种损害记忆的进行性神经退行性疾病。在这里,我们使用模式生物黑腹果蝇研究了淀粉样前体蛋白样蛋白(APPL)的作用。在本研究中,Appl基因敲除突变体在正常条件下寿命缩短,甘油三酯水平升高,而二甲双胍治疗可缓解这些症状。此外,Appl突变体的味觉联想记忆损伤表明APPL在记忆形成中发挥作用,补充姜黄素可恢复这种作用。Appl突变体还表现出攀爬能力下降,补充维生素C(抗坏血酸)和维生素B(核黄素)可改善这一情况。这些发现表明APPL参与了黑腹果蝇的代谢调节、认知、攀爬活动和衰老过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a084/11697555/e61e52158ee3/gr1.jpg

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