Wang Jiayuan, Wang Xinyu, An Zihui, Wang Xuan, Wang Yaru, Lu Yuehan, Qiu Mengsheng, Liu Zheqi, Tan Zhou
Zhejiang Key Laboratory of Organ Development and Regeneration, School of Life and Environmental Science, Hangzhou Normal University, Hangzhou311121, China.
Zhejiang Chinese Medical University, Hangzhou TCM Hospital, Hangzhou, 311121, China.
Curr Alzheimer Res. 2024 Dec 2. doi: 10.2174/0115672050345431241113112608.
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting the central nervous system (CNS), with its etiology still shrouded in uncertainty. The interplay of extracellular amyloid-β (Aβ) deposition, intracellular neurofibrillary tangles (NFTs) composed of tau protein, cholinergic neuronal impairment, and other pathogenic factors is implicated in the progression of AD.
The current study endeavors to delineate the proteomic landscape alterations in the hippocampus of an AD murine model, utilizing proteomic analysis to identify key physiological and pathological shifts induced by the disease. This endeavor aims to shed light on the underlying pathogenic mechanisms, which could facilitate early diagnosis and pave the way for novel therapeutic interventions for AD.
To dissect the proteomic perturbations induced by Aβ and Presenilin-1 (PS1) in the AD pathogenesis, we undertook a label-free quantitative (LFQ) proteomic analysis focusing on the hippocampal proteome of the APP/PS1 transgenic mouse model. Employing a multi-faceted approach that included differential protein functional enrichment, cluster analysis, and protein-protein interaction (PPI) network analysis, we conducted a comprehensive comparative proteomic study between APP/PS1 transgenic mice and their wild-type C57BL/6 counterparts.
Mass spectrometry identified a total of 4817 proteins in the samples, with 2762 proteins being quantifiable. Comparative analysis revealed 396 proteins with differential expression between the APP/PS1 and control groups. Notably, 35 proteins exhibited consistent temporal regulation trends in the hippocampus, with concomitant alterations in biological pathways and PPI networks.
This study presents a comparative proteomic profile of transgenic (APP/PS1) and wild-type mice, highlighting the proteomic divergences. Furthermore, it charts the trajectory of proteomic changes in the AD mouse model across the developmental stages from 2 to 12 months, providing insights into the physiological and pathological implications of the disease-associated genetic mutations.
阿尔茨海默病（AD）是一种影响中枢神经系统（CNS）的常见神经退行性疾病，其病因仍不明朗。细胞外淀粉样β蛋白（Aβ）沉积、由tau蛋白组成的细胞内神经原纤维缠结（NFTs）、胆碱能神经元损伤及其他致病因素之间的相互作用与AD的进展有关。
本研究旨在描绘AD小鼠模型海马体中的蛋白质组图谱变化，利用蛋白质组分析来识别该疾病引起的关键生理和病理变化。这一努力旨在阐明潜在的致病机制，从而有助于早期诊断，并为AD的新型治疗干预铺平道路。
为剖析Aβ和早老素1（PS1）在AD发病机制中引起的蛋白质组扰动，我们对APP/PS1转基因小鼠模型的海马体蛋白质组进行了无标记定量（LFQ）蛋白质组分析。采用包括差异蛋白质功能富集、聚类分析和蛋白质-蛋白质相互作用（PPI）网络分析在内的多方面方法，我们对APP/PS1转基因小鼠及其野生型C57BL/6对照小鼠进行了全面的比较蛋白质组研究。
质谱分析在样本中总共鉴定出4817种蛋白质，其中2762种蛋白质可定量。比较分析显示APP/PS1组和对照组之间有396种蛋白质表达存在差异。值得注意的是，35种蛋白质在海马体中呈现出一致的时间调控趋势，同时生物途径和PPI网络也发生了相应变化。
本研究展示了转基因（APP/PS1）小鼠和野生型小鼠的比较蛋白质组图谱，突出了蛋白质组的差异。此外，它描绘了AD小鼠模型在2至12个月发育阶段的蛋白质组变化轨迹，为与疾病相关的基因突变的生理和病理意义提供了见解。
