Redox proteomics and amyloid β-peptide: insights into Alzheimer disease.
Redox proteomics and amyloid β-peptide: insights into Alzheimer disease.
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DOI：
10.1111/jnc.14589
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发表时间：
2019-11
影响因子：
4.7
通讯作者：
Boyd-Kimball D
中科院分区：
文献类型：
--
作者：
Butterfield DA;Boyd-Kimball D
阿尔茨海默病（Alzheimer disease，AD）是一种与衰老相关的进行性神经退行性疾病，其病理特征为存在老年斑、神经元缠结以及神经突和突触丢失。淀粉样β-肽（1-42）[Aβ（1-42）]是老年斑的主要成分，具有神经毒性，在体外和体内均可诱导氧化应激。氧化还原蛋白质组学已被用于在体外和体内鉴定被Aβ（1-42）氧化修饰的蛋白质。在这篇综述中，我们讨论了这些蛋白的背景下，被确定为被氧化修饰的AD动物模型，和人类的研究，包括家族性AD（FAD），临床前AD（PCAD），轻度认知障碍（MCI），早期AD（EAD），晚期AD（LAD），唐氏综合征（DS）和DS与AD（DS/AD）。这些氧化还原蛋白质组学研究表明，Aβ（1-42）介导的氧化应激发生在AD发病机制的早期，并导致抗氧化和细胞解毒防御功能改变、能量产生代谢降低和线粒体功能障碍、兴奋性毒性、突触可塑性和细胞结构丧失、神经炎症、蛋白质折叠和降解受损以及信号转导改变。改善生物标志物成像的可及性以及确定减少Aβ产生的生活方式干预或治疗可能有助于预防或延缓AD的进展。在这篇综述中，我们讨论了氧化还原蛋白质组学如何提供洞察Aβ（1-42）介导的细胞死亡在阿尔茨海默病（AD）及其早期阶段，遗忘型轻度认知障碍（MCI），以及在体外和体内模型，如何启动脂质过氧化反应。寡聚体Aβ（1-42）嵌入脂质双层中，诱导脂质过氧化，产生反应性4-羟基-2-壬烯醛（HNE）。HNE通过Michael加成作用与蛋白质上的Cys、His和Lys残基共价结合，改变蛋白质的构象并降低其功能。通过氧化还原蛋白质组学鉴定，由于Aβ（1-42）介导的HNE修饰而导致脑中受损和功能障碍的关键过程是葡萄糖代谢、突触可塑性、突触谷氨酸清除和蛋白质稳态，最终导致神经元死亡。
Alzheimer disease (AD) is a progressive neurodegenerative disorder associated with aging and characterized pathologically by the presence of senile plaques, neurofibrillary tangles, and neurite and synapse loss. Amyloid beta-peptide (1–42) [Aβ(1–42)], a major component of senile plaques, is neurotoxic and induces oxidative stress in vitro and in vivo. Redox proteomics has been used to identify proteins oxidatively modified by Aβ(1–42) in vitro and in vivo. In this review, we discuss these proteins in the context of those identified to be oxidatively modified in animal models of AD, and human studies including Familial AD (FAD), Preclinical AD (PCAD), Mild Cognitive Impairment (MCI), Early AD (EAD), Late AD (LAD), Down syndrome (DS) and DS with AD (DS/AD). These redox proteomics studies indicate that Aβ(1–42)-mediated oxidative stress occurs early in AD pathogenesis and results in altered antioxidant and cellular detoxification defenses, decreased energy yielding metabolism and mitochondrial dysfunction, excitotoxicity, loss of synaptic plasticity and cell structure, neuroinflammation, impaired protein folding and degradation, and altered signal transduction. Improved access to biomarker imaging and the identification of lifestyle interventions or treatments to reduce Aβ production could be beneficial in preventing or delaying the progression of AD. In this review we discuss how redox proteomics provided insights into how Aβ(1–42)-mediated cell death in Alzheimer disease (AD) and its earlier stage, amnestic mild cognitive impairment (MCI), and in in vitro and in vivo models thereof, is initiated by lipid peroxidation. Oligomeric Aβ(1–42) embeds in the lipid bilayer inducing lipid peroxidation, leading to reactive 4-hydroxy-2-nonenal (HNE). HNE covalently binds Cys, His, and Lys residues on proteins by Michael addition, changing the proteins’ conformation and decreasing their function. Key processes in brain that are damaged and dysfunctional as a result of Aβ(1–42)-mediated HNE modification identified by redox proteomics are glucose metabolism, synaptic plasticity, synaptic glutamate clearance, and proteostasis, ultimately leading to neuronal death.
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影响因子：
6.1
作者：
Aluise CD;Robinson RA;Beckett TL;Murphy MP;Cai J;Pierce WM;Markesbery WR;Butterfield DA
通讯作者：
Butterfield DA
DOI：
10.1042/bcj20160082
发表时间：
2016-08-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Bishop P;Rocca D;Henley JM
通讯作者：
Henley JM
影响因子：
3.3
作者：
Aksenov, MY;Aksenova, MV;Markesbery, WR
通讯作者：
Markesbery, WR
影响因子：
14
作者：
通讯作者：
--
影响因子：
4
作者：
Area-Gomez E;Schon EA
通讯作者：
Schon EA