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Making extra room for carotenoids in plant cells: New opportunities for biofortification 在植物细胞中为类胡萝卜素创造额外的空间:生物强化的新机会
IF 13.6 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-11-01 DOI: 10.1016/j.plipres.2021.101128
Salvador Torres-Montilla, Manuel Rodriguez-Concepcion

Plant carotenoids are essential for photosynthesis and photoprotection and provide colors in the yellow to red range to non-photosynthetic organs such as petals and ripe fruits. They are also the precursors of biologically active molecules not only in plants (including hormones and retrograde signals) but also in animals (including retinoids such as vitamin A). A carotenoid-rich diet has been associated with improved health and cognitive capacity in humans, whereas the use of carotenoids as natural pigments is widespread in the agrofood and cosmetic industries. The nutritional and economic relevance of carotenoids has spurred a large number of biotechnological strategies to enrich plant tissues with carotenoids. Most of such approaches to alter carotenoid contents in plants have been focused on manipulating their biosynthesis or degradation, whereas improving carotenoid sink capacity in plant tissues has received much less attention. Our knowledge on the molecular mechanisms influencing carotenoid storage in plants has substantially grown in the last years, opening new opportunities for carotenoid biofortification. Here we will review these advances with a particular focus on those creating extra room for carotenoids in plant cells either by promoting the differentiation of carotenoid-sequestering structures within plastids or by transferring carotenoid production to the cytosol.

植物类胡萝卜素对光合作用和光保护至关重要,并为非光合作用器官(如花瓣和成熟果实)提供黄色到红色的颜色。它们也是生物活性分子的前体,不仅存在于植物中(包括激素和逆行信号),也存在于动物中(包括维生素A等类维生素A)。富含类胡萝卜素的饮食与改善人类的健康和认知能力有关,而类胡萝卜素作为天然色素的使用在农业食品和化妆品工业中广泛使用。类胡萝卜素的营养和经济意义促使大量生物技术策略用类胡萝卜素丰富植物组织。大多数改变植物中类胡萝卜素含量的方法都集中在控制它们的生物合成或降解上,而提高植物组织中类胡萝卜素的吸收能力却很少受到关注。我们对影响植物类胡萝卜素储存的分子机制的了解在过去几年中有了实质性的增长,为类胡萝卜素生物强化开辟了新的机会。在这里,我们将回顾这些进展,特别关注那些通过促进质体内类胡萝卜素隔离结构的分化或通过将类胡萝卜素生产转移到细胞质中,在植物细胞中为类胡萝卜素创造额外空间的进展。
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引用次数: 21
Imaging lipids in biological samples with surface-assisted laser desorption/ionization mass spectrometry: A concise review of the last decade 表面辅助激光解吸/电离质谱成像生物样品中的脂质:近十年的简要回顾
IF 13.6 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-07-01 DOI: 10.1016/j.plipres.2021.101114
Wendy H. Müller, Edwin De Pauw, Johann Far, Cedric Malherbe, Gauthier Eppe

Knowing the spatial location of the lipid species present in biological samples is of paramount importance for the elucidation of pathological and physiological processes. In this context, mass spectrometry imaging (MSI) has emerged as a powerful technology allowing the visualization of the spatial distributions of biomolecules, including lipids, in complex biological samples. Among the different ionization methods available, the emerging surface-assisted laser desorption/ionization (SALDI) MSI offers unique capabilities for the study of lipids. This review describes the specific advantages of SALDI-MSI for lipid analysis, including the ability to perform analyses in both ionization modes with the same nanosubstrate, the detection of lipids characterized by low ionization efficiency in MALDI-MS, and the possibilities of surface modification to improve the detection of lipids. The complementarity of SALDI and MALDI-MSI is also discussed. Finally, this review presents data processing strategies applied in SALDI-MSI of lipids, as well as examples of applications of SALDI-MSI in biomedical lipidomics.

了解生物样品中存在的脂质种类的空间位置对于阐明病理和生理过程至关重要。在这种背景下,质谱成像(MSI)已经成为一种强大的技术,允许在复杂的生物样品中可视化生物分子的空间分布,包括脂质。在可用的不同电离方法中,新兴的表面辅助激光解吸/电离(SALDI) MSI为脂质研究提供了独特的能力。这篇综述描述了SALDI-MSI在脂质分析方面的特殊优势,包括在两种电离模式下使用相同的纳米底物进行分析的能力,在MALDI-MS中检测以低电离效率为特征的脂质,以及表面修饰以提高脂质检测的可能性。并讨论了SALDI和MALDI-MSI的互补性。最后,本文综述了SALDI-MSI在脂质数据处理中的应用策略,以及SALDI-MSI在生物医学脂质组学中的应用实例。
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引用次数: 14
Molecular insights into lipoxygenases for biocatalytic synthesis of diverse lipid mediators 生物催化合成多种脂质介质的脂氧合酶分子研究
IF 13.6 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-07-01 DOI: 10.1016/j.plipres.2021.101110
Jung-Ung An , Seong-Eun Kim , Deok-Kun Oh

Oxylipins derived mainly from C20- and C22-polyunsaturated fatty acids (PUFAs), termed lipid mediators (LMs), are essential signalling messengers involved in human physiological responses associated with homeostasis and healing process for infection and inflammation. Some LMs involved in the resolution of inflammation and infection are termed specialized pro-resolving mediators (SPMs), which are generated by human M2 macrophages or polymorphonuclear leukocytes and have the potential to protect and treat hosts from bacterial and viral infections by phagocytosis activation. Lipoxygenases (LOXs) biosynthesize regio- and stereoselective LMs. Thus, understanding the regio- and stereoselectivities of LOXs for PUFAs at a molecular level is important for the biocatalytic synthesis of diverse LMs. Here, we elucidate the catalytic mechanisms and discuss regio- and stereoselectivities and their changes of LOXs determined by insertion direction and position of the substrate and oxygen at a molecular level for the biosynthesis of diverse human LMs. Recently, the biocatalytic synthesis of PUFAs to human LMs or analogues has been conducted using microbial LOXs. Such microbial LOXs involved in the biosynthesis of LMs are expected to exert significantly higher activity and stability than human LOXs. Diverse regio- and stereoselective LOXs can be obtained from microorganisms, which represent a wealth of genomic sources. We reconstruct the biosynthetic pathways of LOX-catalyzed LMs in humans and other organisms. Furthermore, we suggest the effective methods of biocatalytic synthesis of diverse human LMs from PUFAs or glucose by using microbial LOXs, increasing the stability and activity of LOXs, combining the reactions of LOXs, and constructing metabolic pathways.

氧化脂素主要来源于C20-和c22多不饱和脂肪酸(PUFAs),被称为脂质介质(LMs),是参与人体生理反应的重要信号信使,与体内平衡和感染和炎症的愈合过程有关。一些参与炎症和感染解决的LMs被称为特化促解决介质(SPMs),它们由人M2巨噬细胞或多形核白细胞产生,具有通过吞噬激活保护和治疗宿主免受细菌和病毒感染的潜力。脂氧合酶(LOXs)生物合成区域选择性和立体选择性脂质。因此,在分子水平上了解LOXs对PUFAs的区域选择性和立体选择性对于多种LMs的生物催化合成具有重要意义。在此,我们从分子水平上阐明了多种人类LMs生物合成的催化机制,并讨论了由底物和氧的插入方向和位置决定的lox的区域选择性和立体选择性及其变化。最近,利用微生物LOXs生物催化合成PUFAs到人LMs或类似物已被进行。这种参与LMs生物合成的微生物lox有望比人类lox具有更高的活性和稳定性。不同的区域选择性和立体选择性lox可以从微生物中获得,这代表了丰富的基因组来源。我们重建了人类和其他生物中lox催化的LMs的生物合成途径。此外,我们还提出了利用微生物LOXs、提高LOXs的稳定性和活性、结合LOXs的反应以及构建代谢途径等生物催化合成多种人类LMs的有效方法。
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引用次数: 24
Regulation of EGFR activation and signaling by lipids on the plasma membrane 质膜上脂质对EGFR激活和信号传导的调控
IF 13.6 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-07-01 DOI: 10.1016/j.plipres.2021.101115
Do-Hyeon Kim , Hong Minh Triet , Sung Ho Ryu

Lipids on the plasma membrane are not only components of the membrane biophysical structures but also regulators of receptor functions. Recently, the critical roles of lipid-protein interactions have been intensively highlighted. Epidermal growth factor receptor (EGFR) is one of the most extensively studied receptors exhibiting various lipid interactions, including interactions with phosphatidylcholine, phosphatidylserine, phosphatidylinositol phosphate, cholesterol, gangliosides, and palmitate. Here, we review recent findings on how direct interaction with these lipids regulates EGFR activation and signaling, providing unprecedented insight into the comprehensive roles of various lipids in the control of EGFR functions. Finally, the current limitations in investigating lipid-protein interactions and novel technologies to potentially overcome these limitations are discussed.

质膜上的脂质不仅是膜生物物理结构的组成部分,而且是受体功能的调节剂。近年来,脂质-蛋白相互作用的关键作用已被广泛关注。表皮生长因子受体(EGFR)是研究最广泛的受体之一,表现出各种脂质相互作用,包括与磷脂酰胆碱、磷脂酰丝氨酸、磷脂酰肌醇磷酸、胆固醇、神经节苷和棕榈酸盐的相互作用。在这里,我们回顾了与这些脂质直接相互作用如何调节EGFR激活和信号传导的最新发现,为各种脂质在控制EGFR功能中的综合作用提供了前所未有的见解。最后,讨论了目前研究脂质-蛋白相互作用的局限性和可能克服这些局限性的新技术。
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引用次数: 10
Fatty acids and evolving roles of their proteins in neurological, cardiovascular disorders and cancers 脂肪酸及其蛋白质在神经系统、心血管疾病和癌症中的进化作用
IF 13.6 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-07-01 DOI: 10.1016/j.plipres.2021.101116
Rahul Mallick , Sanjay Basak , Asim K. Duttaroy

The dysregulation of fat metabolism is involved in various disorders, including neurodegenerative, cardiovascular, and cancers. The uptake of long-chain fatty acids (LCFAs) with 14 or more carbons plays a pivotal role in cellular metabolic homeostasis. Therefore, the uptake and metabolism of LCFAs must constantly be in tune with the cellular, metabolic, and structural requirements of cells. Many metabolic diseases are thought to be driven by the abnormal flow of fatty acids either from the dietary origin and/or released from adipose stores. Cellular uptake and intracellular trafficking of fatty acids are facilitated ubiquitously with unique combinations of fatty acid transport proteins and cytoplasmic fatty acid-binding proteins in every tissue. Extensive data are emerging on the defective transporters and metabolism of LCFAs and their clinical implications. Uptake and metabolism of LCFAs are crucial for the brain's functional development and cardiovascular health and maintenance. In addition, data suggest fatty acid metabolic transporter can normalize activated inflammatory response by reprogramming lipid metabolism in cancers.

Here we review the current understanding of how LCFAs and their proteins contribute to the pathophysiology of three crucial diseases and the mechanisms involved in the processes.

脂肪代谢失调与多种疾病有关,包括神经退行性疾病、心血管疾病和癌症。含有14个或更多碳的长链脂肪酸(LCFAs)的摄取在细胞代谢稳态中起着关键作用。因此,LCFAs的摄取和代谢必须始终与细胞的细胞、代谢和结构需求保持一致。许多代谢疾病被认为是由来自饮食来源和/或从脂肪储存中释放的脂肪酸的异常流动所驱动的。脂肪酸的细胞摄取和细胞内运输在每个组织中都通过脂肪酸转运蛋白和细胞质脂肪酸结合蛋白的独特组合来促进。关于LCFAs的缺陷转运体和代谢及其临床意义的大量数据正在出现。LCFAs的摄取和代谢对大脑功能发育和心血管健康和维持至关重要。此外,数据表明脂肪酸代谢转运蛋白可以通过重编程癌症的脂质代谢使激活的炎症反应正常化。在这里,我们回顾了目前对LCFAs及其蛋白如何参与三种关键疾病的病理生理以及该过程所涉及的机制的理解。
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引用次数: 32
Plasmalogens - Ubiquitous molecules occurring widely, from anaerobic bacteria to humans 等离子原-广泛存在的分子,从厌氧细菌到人类
IF 13.6 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-07-01 DOI: 10.1016/j.plipres.2021.101111
Milada Vítová , Andrea Palyzová , Tomáš Řezanka

Plasmalogens are a group of lipids mainly found in the cell membranes. They occur in anaerobic bacteria and in some protozoa, invertebrates and vertebrates, including humans. Their occurrence in plants and fungi is controversial. They can protect cells from damage by reactive oxygen species, protect other phospholipids or lipoprotein particles against oxidative stress, and have been implicated as signaling molecules and modulators of membrane dynamics. Biosynthesis in anaerobic and aerobic organisms occurs by different pathways, and the main biosynthetic pathway in anaerobic bacteria was clarified only this year (2021). Many different analytical techniques have been used for plasmalogen analysis, some of which are detailed below. These can be divided into two groups: shotgun lipidomics, or electrospray ionization mass spectrometry in combination with high performance liquid chromatography (LC-MS). The advantages and limitations of both techniques are discussed here, using examples from anaerobic bacteria to specialized mammalian (human) organs.

缩醛原是一组主要存在于细胞膜中的脂质。它们存在于厌氧菌和一些原生动物、无脊椎动物和脊椎动物中,包括人类。它们在植物和真菌中的存在是有争议的。它们可以保护细胞免受活性氧的损伤,保护其他磷脂或脂蛋白颗粒免受氧化应激,并作为信号分子和膜动力学调节剂。厌氧和好氧生物的生物合成通过不同的途径进行,厌氧菌的主要生物合成途径直到今年(2021年)才被阐明。许多不同的分析技术已用于分析等离子体原,其中一些详细介绍如下。这些可分为两组:霰弹枪脂质组学,或结合高效液相色谱(LC-MS)的电喷雾电离质谱。本文讨论了这两种技术的优点和局限性,使用了从厌氧细菌到专门的哺乳动物(人类)器官的例子。
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引用次数: 11
Potential modulatory mechanisms of action by long-chain polyunsaturated fatty acids on bone cell and chondrocyte metabolism 长链多不饱和脂肪酸对骨细胞和软骨细胞代谢的潜在调节机制
IF 13.6 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-07-01 DOI: 10.1016/j.plipres.2021.101113
Maryam Abshirini, Bolaji Lilian Ilesanmi-Oyelere, Marlena C. Kruger

Long-chain polyunsaturated fatty acids (LCPUFAs) and their metabolites are considered essential factors to support bone and joint health. The n-6 PUFAs suppress the osteoblasts differentiation via increasing peroxisome proliferator-activated receptor gamma (PPARγ) expression and promoting adipogenesis while n-3 PUFAs promote osteoblastogenesis by down-regulating PPARγ and enhancing osteoblastic activity. Arachidonic acid (AA) and its metabolite prostaglandin E2 (PGE2) are key regulators of osteoclast differentiation via induction of the receptor activator of nuclear factor kappa-Β ligand (RANKL) pathway. Marine-derived n-3 LCPUFAs have been shown to inhibit osteoclastogenesis by decreasing the osteoprotegerin (OPG)/RANKL signalling pathway mediated by a reduction of pro-inflammatory PGE2 derived from AA. Omega-3 PUFAs reduce the expression of cartilage degrading enzyme matrix metalloproteinase-13 (MMP-13) and a disintegrin and metalloprotease with thrombospondin motifs-5 (ADAMTS-5) protein, oxidative stress and thereby apoptosis via nuclear factor kappa-betta (NF-kβ) and inducible nitric oxide synthase (iNOS) pathways. In this review, a diverse range of important effects of LCPUFAs on bone cells and chondrocyte was highlighted through different mechanisms of action established by cell cultures and animal studies. This review allows a better understanding of the possible role of LCPUFAs in bone and chondrocyte metabolism as potential therapeutics in combating the pathological complications such as osteoporosis and osteoarthritis.

长链多不饱和脂肪酸(LCPUFAs)及其代谢产物被认为是支持骨骼和关节健康的必要因素。n-6 PUFAs通过增加过氧化物酶体增殖物激活受体γ (PPARγ)的表达和促进脂肪形成来抑制成骨细胞的分化,而n-3 PUFAs通过下调PPARγ和增强成骨细胞活性来促进成骨细胞的形成。花生四烯酸(AA)及其代谢物前列腺素E2 (PGE2)通过诱导核因子κ pa-Β配体(RANKL)途径受体激活物,是破骨细胞分化的关键调控因子。海洋来源的n-3 LCPUFAs已被证明通过减少AA来源的促炎PGE2介导的骨保护素(OPG)/RANKL信号通路来抑制破骨细胞的发生。Omega-3 PUFAs通过核因子κ β (NF-kβ)和诱导型一氧化氮合酶(iNOS)途径降低软骨降解酶基质金属蛋白酶-13 (MMP-13)和崩解素金属蛋白酶-5 (ADAMTS-5)蛋白的表达、氧化应激和细胞凋亡。在这篇综述中,通过细胞培养和动物研究建立的不同作用机制,强调了LCPUFAs对骨细胞和软骨细胞的多种重要作用。这篇综述可以更好地理解LCPUFAs在骨和软骨细胞代谢中的可能作用,作为对抗骨质疏松症和骨关节炎等病理并发症的潜在治疗药物。
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引用次数: 37
Hepatic cholesterol transport and its role in non-alcoholic fatty liver disease and atherosclerosis 肝脏胆固醇转运及其在非酒精性脂肪性肝病和动脉粥样硬化中的作用
IF 13.6 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-07-01 DOI: 10.1016/j.plipres.2021.101109
Heng Li , Xiao-Hua Yu , Xiang Ou , Xin-Ping Ouyang , Chao-Ke Tang

Non-alcoholic fatty liver disease (NAFLD) is a quickly emerging global health problem representing the most common chronic liver disease in the world. Atherosclerotic cardiovascular disease represents the leading cause of mortality in NAFLD patients. Cholesterol metabolism has a crucial role in the pathogenesis of both NAFLD and atherosclerosis. The liver is the major organ for cholesterol metabolism. Abnormal hepatic cholesterol metabolism not only leads to NAFLD but also drives the development of atherosclerotic dyslipidemia. The cholesterol level in hepatocytes reflects the dynamic balance between endogenous synthesis, uptake, esterification, and export, a process in which cholesterol is converted to neutral cholesteryl esters either for storage in cytosolic lipid droplets or for secretion as a major constituent of plasma lipoproteins, including very-low-density lipoproteins, chylomicrons, high-density lipoproteins, and low-density lipoproteins. In this review, we describe decades of research aimed at identifying key molecules and cellular players involved in each main aspect of hepatic cholesterol metabolism. Furthermore, we summarize the recent advances regarding the biological processes of hepatic cholesterol transport and its role in NAFLD and atherosclerosis.

非酒精性脂肪性肝病(NAFLD)是一个迅速出现的全球健康问题,代表了世界上最常见的慢性肝病。动脉粥样硬化性心血管疾病是NAFLD患者死亡的主要原因。胆固醇代谢在NAFLD和动脉粥样硬化的发病机制中都起着至关重要的作用。肝脏是胆固醇代谢的主要器官。肝脏胆固醇代谢异常不仅会导致NAFLD,还会推动动脉粥样硬化性血脂异常的发展。肝细胞内的胆固醇水平反映了内源性合成、摄取、酯化和输出之间的动态平衡。在这个过程中,胆固醇被转化为中性胆固醇酯,要么储存在细胞质脂滴中,要么作为血浆脂蛋白的主要成分分泌,包括极低密度脂蛋白、乳糜微粒、高密度脂蛋白和低密度脂蛋白。在这篇综述中,我们描述了几十年来的研究,旨在确定参与肝脏胆固醇代谢的每个主要方面的关键分子和细胞参与者。此外,我们总结了肝脏胆固醇转运的生物学过程及其在NAFLD和动脉粥样硬化中的作用的最新进展。
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引用次数: 69
Phosphatidylserine-specific phospholipase A1: A friend or the devil in disguise 磷脂酰丝氨酸特异性磷脂酶A1:是朋友还是伪装的魔鬼
IF 13.6 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-07-01 DOI: 10.1016/j.plipres.2021.101112
Yang Zhao, Stephan Hasse, Sylvain G. Bourgoin

Various human tissues and cells express phospholipase A1 member A (PLA1A), including the liver, lung, prostate gland, and immune cells. The enzyme belongs to the pancreatic lipase family. PLA1A specifically hydrolyzes sn-1 fatty acid of phosphatidylserine (PS) or 1-acyl-lysophosphatidylserine (1-acyl-lysoPS). PS externalized by activated cells or apoptotic cells or extracellular vesicles is a potential source of substrate for the production of unsaturated lysoPS species by PLA1A. Maturation and functions of many immune cells, such as T cells, dendritic cells, macrophages, and mast cells, can be regulated by PLA1A and lysoPS. Several lysoPS receptors, including GPR34, GPR174 and P2Y10, have been identified. High serum levels and high PLA1A expression are associated with autoimmune disorders such as Graves' disease and systemic lupus erythematosus. Increased expression of PLA1A is associated with metastatic melanomas. PLA1A may contribute to cardiometabolic disorders through mediating cholesterol transportation and producing lysoPS. Furthermore, PLA1A is necessary for hepatitis C virus assembly and can play a role in the antivirus innate immune response. This review summarizes recent findings on PLA1A expression, lysoPS and lysoPS receptors in autoimmune disorders, cancers, cardiometabolic disorders, antivirus immune responses, as well as regulations of immune cells.

多种人体组织和细胞表达磷脂酶A1成员A (PLA1A),包括肝脏、肺、前列腺和免疫细胞。这种酶属于胰脂肪酶家族。PLA1A特异水解sn-1脂肪酸的磷脂酰丝氨酸(PS)或1-酰基-溶血磷脂酰丝氨酸(1-酰基-溶血ops)。活化细胞或凋亡细胞或细胞外囊泡外化的PS是PLA1A产生不饱和溶酶产物的潜在底物来源。许多免疫细胞的成熟和功能,如T细胞、树突状细胞、巨噬细胞和肥大细胞,都可以通过PLA1A和lysoPS来调节。已鉴定出几种溶酶ops受体,包括GPR34、GPR174和P2Y10。高血清水平和高PLA1A表达与自身免疫性疾病如格雷夫斯病和系统性红斑狼疮有关。PLA1A表达增加与转移性黑色素瘤有关。PLA1A可能通过介导胆固醇运输和产生溶酶ops而导致心脏代谢紊乱。此外,PLA1A是丙型肝炎病毒组装所必需的,可以在抗病毒先天免疫反应中发挥作用。本文综述了PLA1A表达、lysoPS和lysoPS受体在自身免疫性疾病、癌症、心脏代谢疾病、抗病毒免疫反应以及免疫细胞调控中的最新研究进展。
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引用次数: 12
Lipid homeostasis and mevalonate pathway in COVID-19: Basic concepts and potential therapeutic targets COVID-19的脂质稳态和甲羟戊酸途径:基本概念和潜在的治疗靶点
IF 13.6 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-04-01 DOI: 10.1016/j.plipres.2021.101099
Maria Chiara Proto , Donatella Fiore , Chiara Piscopo , Cristina Pagano , Mario Galgani , Sara Bruzzaniti , Chiara Laezza , Patrizia Gazzerro , Maurizio Bifulco

Despite encouraging progresses achieved in the management of viral diseases, efficient strategies to counteract infections are still required. The current global challenge highlighted the need to develop a rapid and cost-effective strategy to counteract the SARS-CoV-2 pandemic.

Lipid metabolism plays a crucial role in viral infections. Viruses can use the host lipid machinery to support their life cycle and to impair the host immune response. The altered expression of mevalonate pathway-related genes, induced by several viruses, assures survival and spread in host tissue. In some infections, statins, HMG-CoA-reductase inhibitors, reduce cholesterol in the plasma membrane of permissive cells resulting in lower viral titers and failure to internalize the virus. Statins can also counteract viral infections through their immunomodulatory, anti-inflammatory and anti-thrombotic effects. Beyond statins, interfering with the mevalonate pathway could have an adjuvant effect in therapies aimed at mitigating endothelial dysfunction and deregulated inflammation in viral infection.

In this review we depicted the historical and current evidence highlighting how lipid homeostasis and mevalonate pathway targeting represents a valid approach to rapidly neutralize viruses, focusing our attention to their potential use as effective targets to hinder SARS-CoV-2 morbidity and mortality.

Pros and cons of statins and Mevalonate-pathway inhibitors have been also dissected.

尽管在病毒性疾病管理方面取得了令人鼓舞的进展,但仍然需要有效的战略来对抗感染。当前的全球挑战突出表明,需要制定一项快速和具有成本效益的战略,以应对SARS-CoV-2大流行。脂质代谢在病毒感染中起关键作用。病毒可以利用宿主的脂质机制来支持它们的生命周期,并削弱宿主的免疫反应。几种病毒诱导甲羟戊酸途径相关基因表达的改变,保证了宿主组织的生存和传播。在某些感染中,他汀类药物、hmg -辅酶a还原酶抑制剂可降低允许细胞质膜中的胆固醇,导致病毒滴度降低,病毒无法内化。他汀类药物还可以通过免疫调节、抗炎和抗血栓作用来对抗病毒感染。除他汀类药物外,干扰甲羟戊酸途径可能在旨在减轻内皮功能障碍和病毒感染中不受调节的炎症的治疗中具有辅助作用。在这篇综述中,我们描述了历史和当前的证据,强调脂质稳态和甲羟戊酸途径靶向是如何快速中和病毒的有效方法,并将我们的注意力集中在它们作为抑制SARS-CoV-2发病率和死亡率的有效靶点的潜在应用上。他汀类药物和甲羟戊酸途径抑制剂的利弊也已被剖析。
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引用次数: 19
期刊
Progress in lipid research
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