Progress in lipid research最新文献_第2页

Physical and oxidative stability of lipid droplets (oleosomes) in seeds and emulsions 种子和乳剂中脂滴（油体）的物理和氧化稳定性

IF 14.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Progress in lipid research

Pub Date : 2025-11-01 DOI: 10.1016/j.plipres.2025.101360

Marie Hennebelle , Lorenz Plankensteiner , Constantinos V. Nikiforidis

Plants have developed a natural solution to a challenge that has long occupied emulsion scientists: how to stably maintain lipids in an aqueous environment while preventing physical and oxidative degradation. Lipid droplets (LDs) are abundant in oilseeds, containing the triacylglycerols (vegetable oils). The physical stability of LDs is ensured by their interface that prevents coalescence, and together with surrounding molecules, protects against oxidation. Despite these advantageous properties of LDs as a whole, industrial vegetable oil extraction often involves the use of organic solvents that dissolve the apolar triacylglycerols, discarding the natural protective mechanism of the LD interfacial molecules. Understanding the structure-function role of the LD interface is essential for inspiring the industrial design of stable emulsions. Our review offers insights into the mechanisms underlying the exceptional stability of LDs in seeds, and after their extraction to create aqueous LD dispersions. We emphasize the key role of the interfacial layer in maintaining their physical stability, in particular through the formation of a dense, elastic network by oleosins, the most abundant proteins on the LD interface. Additionally, we highlight the multi-layered antioxidant system developed by seeds to protect LDs from oxidation, comprising both intrinsic (tocopherols) and extrinsic (phenolics and storage proteins) components.

植物已经开发出一种天然的解决方案来解决长期困扰乳剂科学家的挑战：如何在水环境中稳定地维持脂质，同时防止物理和氧化降解。油籽中含有丰富的脂滴（ld），含有三酰基甘油（植物油）。ld的物理稳定性由其防止聚结的界面保证，并与周围分子一起防止氧化。尽管LD整体上具有这些优点，但工业植物油提取通常涉及使用溶解极性三酰基甘油的有机溶剂，从而丢弃了LD界面分子的自然保护机制。了解LD界面的结构-功能作用对于激发稳定乳剂的工业设计至关重要。我们的综述提供了对种子中LD的特殊稳定性的机制的见解，以及它们在提取后形成水溶LD分散体的机制。我们强调了界面层在维持其物理稳定性方面的关键作用，特别是通过油蛋白（LD界面上最丰富的蛋白质）形成致密的弹性网络。此外，我们强调了由种子开发的多层抗氧化系统，以保护ld免受氧化，包括内在（生育酚）和外在（酚类物质和储存蛋白）成分。

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引用次数: 0

PLA2G4E in health and disease: Insights from omics and functional analyses PLA2G4E在健康和疾病中的作用：来自组学和功能分析的见解

IF 14.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Progress in lipid research

Pub Date : 2025-11-01 DOI: 10.1016/j.plipres.2025.101359

Maša Čater , Martin Šimon , Nicholas M. Morton , Tanja Kunej , Simon Horvat

The phospholipase A₂ (PLA₂) enzyme superfamily has been extensively studied, but comprehensive reviews on cytosolic phospholipase A₂ group IVE (PLA2G4E) remain scarce, limiting our understanding of its role in lipid metabolism and disease. Our review synthesizes current findings on the human PLA2G4E gene and its murine ortholog Pla2g4e, drawing from multi-omics analyses and a range of functional studies. Pla2g4e exhibits distinct expression patterns across tissues, suggesting potential tissue-specific roles. In addition to its phospholipase activity, PLA2G4E exhibits N-acyltransferase activity and responds to calcium influx. Emerging evidence suggests possible involvement in metabolic disorders such as obesity and diabetes, particularly through effects on glucose uptake and insulin sensitivity. PLA2G4E has been implicated in the synthesis of N-acylethanolamines with potential effects on energy homeostasis, stress adaptation, neuronal signaling, pain perception, cognition, and motor coordination. Genomic and preliminary functional evidence further point to possible roles in immune regulation and neurobiology, with some associations reported in neurodegenerative diseases such as Alzheimer's disease. Comprehensive insights into the biological roles of PLA2G4E are essential for clarifying its enzymatic functions and potential involvement in disease mechanisms; however, further experimental and clinical studies are needed to substantiate these emerging associations and assess its therapeutic potential.

磷脂酶A2 （PLA2）酶超家族已经被广泛研究，但对细胞质磷脂酶A2组IVE （PLA2G4E）的全面综述仍然很少，限制了我们对其在脂质代谢和疾病中的作用的理解。我们的综述综合了人类PLA2G4E基因及其小鼠同源基因PLA2G4E的最新发现，这些发现来自多组学分析和一系列功能研究。Pla2g4e在不同组织中表现出不同的表达模式，表明其具有潜在的组织特异性作用。除了磷脂酶活性外，PLA2G4E还表现出n -酰基转移酶活性并对钙内流作出反应。新出现的证据表明，它可能参与代谢紊乱，如肥胖和糖尿病，特别是通过对葡萄糖摄取和胰岛素敏感性的影响。PLA2G4E与n -酰基乙醇胺的合成有关，对能量稳态、应激适应、神经元信号传导、疼痛感知、认知和运动协调有潜在影响。基因组和初步的功能证据进一步指出，在免疫调节和神经生物学中可能起作用，在阿尔茨海默病等神经退行性疾病中也有一些关联。全面了解PLA2G4E的生物学作用对于阐明其酶功能及其在疾病机制中的潜在参与至关重要；然而，需要进一步的实验和临床研究来证实这些新出现的关联并评估其治疗潜力。

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引用次数: 0

Roles of prostaglandin signaling in implantation and decidualization 前列腺素信号在植入和去个体化中的作用。

IF 14.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Progress in lipid research

Pub Date : 2025-10-01 DOI: 10.1016/j.plipres.2025.101357

Yukihiko Sugimoto , Shizu Aikawa , Tomoaki Inazumi , Yasushi Hirota

Embryo implantation and subsequent decidualization are crucial processes for the establishment of a healthy pregnancy, but the molecular mechanisms underlying these processes remain unclear. Prostaglandins (PGs), which are synthesized from arachidonic acid via a pathway involving cyclooxygenase (COX) as the rate-limiting enzyme, have been shown to regulate implantation. Recently, the COX isozymes COX-1 and COX-2 were found to play distinct roles in implantation. Furthermore, the PG receptors involved in decidualization have been identified. In this review, we summarize the role of PGs in implantation from the viewpoint of COX and PG receptors, as well as the interplay between PGs and lysophosphatidic acid upon embryo implantation.

胚胎着床和随后的脱卵化是建立健康妊娠的关键过程，但这些过程背后的分子机制尚不清楚。前列腺素（PGs）是花生四烯酸通过环氧化酶（COX）作为限速酶的途径合成的，已被证明可以调节着床。近年来，COX同工酶COX-1和COX-2被发现在着床过程中发挥着不同的作用。此外，PG受体参与去个体化已被确定。本文从COX和PG受体的角度综述了PG在胚胎着床中的作用，以及PG与溶血磷脂酸在胚胎着床中的相互作用。

引用次数: 0

Omega-3 polyunsaturated fatty acids in neurodegenerative disorders: Mixed designs = mixed results 神经退行性疾病中的Omega-3多不饱和脂肪酸：混合设计 = 混合结果。

IF 14.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Progress in lipid research

Pub Date : 2025-09-19 DOI: 10.1016/j.plipres.2025.101356

Simon C. Dyall , Mélanie Plourde

Epidemiological studies consistently show an elevated intake of fish and long-chain omega-3 polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), reduces the risk of developing neurodegenerative diseases, particularly dementia and Alzheimer's disease. These observations are supported by preclinical research, where a range of potential mechanisms have been identified, such as increasing neurogenesis, or regulating inflammation and neuroinflammation via the production of bioactive lipid mediators. However, the results of clinical trials have been inconsistent and mixed, and this may be due to the considerable heterogeneity in trial designs, but also a lack of appreciation of methodological complications unique to omega-3 PUFA research. In this review, we explore omega-3 PUFA specific methodological considerations based around participant selection and trial design. Participant-related aspects include baseline cognitive status, age, sex and genotype, whereas methodological aspects include placebo selection, DHA vs. EPA, chemical form and quality of the omega-3 PUFA preparation, and wider nutrient interactions. We also suggest how consideration of these factors should be included in the design and reporting of clinical trials, with the aim of increasing the validity and reproducibility of research in the field.

流行病学研究一致表明，增加鱼类和长链omega-3多不饱和脂肪酸（PUFAs）的摄入量，如二十二碳六烯酸（DHA）和二十碳五烯酸（EPA），可以降低患神经退行性疾病的风险，特别是痴呆症和阿尔茨海默病。这些观察结果得到了临床前研究的支持，其中已经确定了一系列潜在的机制，例如增加神经发生，或通过产生生物活性脂质介质调节炎症和神经炎症。然而，临床试验的结果是不一致和混杂的，这可能是由于试验设计的相当大的异质性，但也缺乏对omega-3 PUFA研究特有的方法学并发症的认识。在这篇综述中，我们探讨了基于参与者选择和试验设计的omega-3 PUFA特定方法学考虑。参与者相关的方面包括基线认知状态、年龄、性别和基因型，而方法学方面包括安慰剂选择、DHA与EPA、omega-3 PUFA制剂的化学形式和质量，以及更广泛的营养相互作用。我们还建议如何在临床试验的设计和报告中考虑这些因素，以提高该领域研究的有效性和可重复性。

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引用次数: 0

Homeocurvature: A new dimension of membrane adaptation to extreme environments 均匀曲率：膜适应极端环境的新维度。

IF 14.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Progress in lipid research

Pub Date : 2025-09-17 DOI: 10.1016/j.plipres.2025.101355

Jacob R. Winnikoff , Itay Budin

Adaptation to abiotic factors is essential for life's radiation across the planet. Lipids, particularly sensitive to pressure and temperature (P and T), play a critical role in biochemical adaptation. In oceanic depths, lower temperatures and increasing hydrostatic pressure influence lipid packing. The prevailing model for lipid response to P and T has been homeoviscosity, regulating membrane viscosity. However, our recent systematic analysis of lipid adaptation in ctenophores revealed an alternative homeocurvature model influenced by the spontaneous curvature of phospholipids. This model highlights pressure as a stronger modulator of lipid curvature than membrane fluidity, which is particularly relevant in deep-sea environments. This review aims to enhance understanding of lipidome responses by synthesizing the challenges posed by extreme P and T. We explore the interplay between homeocurvature and homeoviscosity, illustrating the unexpected genesis of the homeocurvature model through chemical and biophysical trends. We apply both models to four published lipidomic datasets from diverse marine taxa, proposing that broader environmental sampling is vital for assessing existing models and discovering new ones. Understanding membrane responses to environmental factors informs the function of cell membranes broadly and helps predict the evolutionary and ecological impacts of global change.

适应非生物因素对整个地球的生命辐射至关重要。脂质对压力和温度（P和T）特别敏感，在生化适应中起着关键作用。在海洋深处，较低的温度和不断增加的静水压力会影响脂质堆积。脂质对P和T反应的主流模型是均匀粘度，调节膜粘度。然而，我们最近对丝团脂质适应的系统分析揭示了另一种受磷脂自发曲率影响的均匀曲率模型。该模型强调压力是比膜流动性更强的脂质曲率调节剂，这在深海环境中尤为重要。本综述旨在通过综合极端P和t带来的挑战来增强对脂质组反应的理解。我们探索了均质曲率和均质粘度之间的相互作用，通过化学和生物物理趋势说明了均质曲率模型的意外起源。我们将这两种模型应用于来自不同海洋分类群的四个已发表的脂质组学数据集，提出更广泛的环境采样对于评估现有模型和发现新模型至关重要。了解细胞膜对环境因素的反应可以广泛地了解细胞膜的功能，并有助于预测全球变化对进化和生态的影响。

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引用次数: 0

Different chains for different gains: How acyl chain diversity shapes S-acylated protein function 不同的链获得不同的收益：酰基链多样性如何塑造s -酰基化蛋白的功能

IF 14.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Progress in lipid research

Pub Date : 2025-09-14 DOI: 10.1016/j.plipres.2025.101354

Carla Busquets Hernández , Alexandra Tsiotsia , Ludovico Pipitò , Luke H. Chamberlain , Jennifer Greaves , Gemma Triola

S-Acylation is a critical post-translational modification involving the attachment of fatty acyl chains to a large and diverse array of soluble and membrane proteins. The last two decades have witnessed a substantial acceleration in our understanding of this process, fuelled by the discovery of acylation enzymes, mapping of the cellular S-acylome, and the development of new chemical biology methodologies to interrogate the mechanisms and functional outcomes of this lipid modification. This modification is often referred to as “S-Palmitoylation”, however mass spectrometry analyses have provided compelling evidence that the acyl chains added to S-acylated proteins are diverse, that site-specific attachment of different acyl chains can be seen, and that exogenous fatty acids can modulate the lipid profile of the S-acylome. This heterogeneity is likely generated through a combination of enzyme specificities, Acyl CoA distribution and availability, and specific features of the modified substrate protein. Despite a limited number of functional studies, acyl chain differences can impact protein localisation and function, and could possibly contribute to the development and progression of disease. It is now clear that recognising and understanding the functional consequences of acyl chain heterogeneity is a pivotal step toward a more complete view of lipid-mediated protein regulation.

s -酰化是一种关键的翻译后修饰，涉及脂肪酰基链附着到大量不同的可溶性和膜蛋白上。在过去的二十年里，我们对这一过程的理解有了实质性的加速，这得益于酰化酶的发现，细胞s -酰基的绘制，以及新的化学生物学方法的发展，以询问这种脂质修饰的机制和功能结果。这种修饰通常被称为“s -棕榈酰化”，然而质谱分析提供了令人信服的证据，证明添加到s -酰化蛋白上的酰基链是多种多样的，可以看到不同酰基链的位点特异性附着，并且外源脂肪酸可以调节s -酰基的脂质谱。这种异质性可能是由酶的特异性、酰基辅酶a的分布和可用性以及修饰底物蛋白的特定特征共同产生的。尽管对功能的研究数量有限，但酰基链的差异可以影响蛋白质的定位和功能，并可能导致疾病的发生和进展。现在很清楚，认识和理解酰基链异质性的功能后果是迈向更完整的脂质介导的蛋白质调节观点的关键一步。

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引用次数: 0

Targeting fatty acid-binding protein 4: A therapeutic intersection of obesity and cancer via lipid metabolism 靶向脂肪酸结合蛋白4：通过脂质代谢治疗肥胖和癌症的交叉

IF 14.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Progress in lipid research

Pub Date : 2025-09-09 DOI: 10.1016/j.plipres.2025.101353

Katarzyna Smolińska , Aleksandra Szopa , Piotr Dobrowolski , Jacek Dziedzic , Norbert Nowak , Anna Serefko , Michał Mirecki , Jan Sobczyński , Timo Ylikomi , Matthias Nees

Fatty acid-binding protein 4 (FABP4) has emerged as a multifunctional regulator in cancer biology, linking dysregulated lipid metabolism, immune modulation, and tumor progression. Initially recognized for its role in fatty acid transport and lipid homeostasis, FABP4 is now understood as a secreted adipokine that influences diverse oncogenic processes, particularly in adipose-rich tumor microenvironments. It is upregulated in various cancers and secreted by both tumor and cancer-associated fibroblasts.

FABP4 facilitates lipid transfer, promotes fatty acid oxidation, and reprograms cancer cell metabolism. It also contributes to the crosstalk between tumor-associated macrophages, T-cells, and dendritic cells. FABP4 also supports epithelial–mesenchymal transition, enhances tumor cell plasticity, promotes invasion and metastasis, and has an impact on therapeutic resistance. The inhibition of FABP4 using small-molecule inhibitors or monoclonal antibodies has shown promise in restoring therapeutic sensitivity and reducing metastasis in preclinical models. FABP4 has emerged as a potential diagnostic and prognostic biomarker that predicts poor outcomes in multiple cancer types, supporting risk stratification and noninvasive diagnostics. Together, these findings place FABP4 at the intersection of tumor metabolism, immune evasion, and therapy resistance, highlighting its potential as both a biomarker and a therapeutic target in precision oncology and personalized medicine.

脂肪酸结合蛋白4 （FABP4）在癌症生物学中作为一种多功能调节剂出现，与脂质代谢失调、免疫调节和肿瘤进展有关。FABP4最初被认为在脂肪酸转运和脂质稳态中起作用，现在被认为是一种影响多种致癌过程的分泌脂肪因子，特别是在富含脂肪的肿瘤微环境中。它在各种癌症中上调，由肿瘤和癌症相关成纤维细胞分泌。FABP4促进脂质转移，促进脂肪酸氧化，并重新编程癌细胞代谢。它还有助于肿瘤相关巨噬细胞、t细胞和树突状细胞之间的串扰。FABP4还支持上皮-间质转化，增强肿瘤细胞可塑性，促进侵袭和转移，并影响治疗耐药性。在临床前模型中，使用小分子抑制剂或单克隆抗体抑制FABP4已显示出恢复治疗敏感性和减少转移的希望。FABP4已成为一种潜在的诊断和预后生物标志物，可预测多种癌症类型的不良预后，支持风险分层和无创诊断。总之，这些发现将FABP4置于肿瘤代谢、免疫逃避和治疗耐药性的交叉点，突出了其作为精确肿瘤学和个性化医学的生物标志物和治疗靶点的潜力。

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引用次数: 0

Apolipoproteins in circulation: At the interface of thrombosis and stroke initiation 循环中的载脂蛋白：在血栓形成和中风起始的界面

IF 14.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Progress in lipid research

Pub Date : 2025-08-18 DOI: 10.1016/j.plipres.2025.101343

Tamara Etuze , Denis Vivien , Fatemeh Dubois

Ischemic stroke, a leading cause of death and disability worldwide, arises predominantly from atherosclerosis and thromboembolic occlusion of cerebral arteries. While advancements in acute interventions such as thrombolysis and thrombectomy have improved outcomes, the identification of upstream molecular drivers remains essential for better prevention and risk stratification. Among these, circulating apolipoproteins, the structural and regulatory proteins of lipoprotein particles, are increasingly recognized as pivotal mediators at the intersection of lipid metabolism, inflammation, endothelial dysfunction and thrombosis.

This review summarizes recent evidence on the diverse roles of apolipoproteins in systemic vascular biology and their contributions to stroke initiation. We examine how specific apolipoproteins influence atherogenesis, plaque instability, coagulation factor dynamics, immune–endothelial interactions and platelet adhesion. Emerging data suggest that functional imbalances among apolipoproteins, independent of conventional lipid levels, may serve as superior predictors of stroke risk and reveal novel mechanistic links between dyslipidemia, immune cell activation and thrombo-inflammation.

By bridging insights from lipidology, vascular biology and thrombosis research, we position apolipoproteins as promising biomarkers and therapeutic targets to reduce the burden of ischemic stroke and improve cerebrovascular health.

缺血性中风是世界范围内死亡和残疾的主要原因，主要由动脉粥样硬化和血栓栓塞性脑动脉闭塞引起。虽然溶栓和取栓等急性干预措施的进展改善了结果，但上游分子驱动因素的识别对于更好地预防和风险分层仍然至关重要。其中，循环载脂蛋白（脂蛋白颗粒的结构和调节蛋白）越来越被认为是脂质代谢、炎症、内皮功能障碍和血栓形成的关键介质。本文综述了载脂蛋白在系统血管生物学中的不同作用及其对卒中起始的贡献的最新证据。我们研究了特定载脂蛋白如何影响动脉粥样硬化、斑块不稳定性、凝血因子动力学、免疫内皮相互作用和血小板粘附。新出现的数据表明，载脂蛋白之间的功能失衡，独立于传统的脂质水平，可能作为中风风险的优越预测因素，并揭示了血脂异常、免疫细胞激活和血栓炎症之间的新的机制联系。通过连接脂质学，血管生物学和血栓研究的见解，我们将载脂蛋白定位为有前途的生物标志物和治疗靶点，以减轻缺血性卒中的负担和改善脑血管健康。

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引用次数: 0

The endocannabinoid system & malignant hyperthermia: From molecular signaling towards clinical implications 内源性大麻素系统与恶性热疗：从分子信号传导到临床意义

IF 14 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Progress in lipid research

Pub Date : 2025-07-01 DOI: 10.1016/j.plipres.2025.101342

Simon Dalle , Sebastiaan Dalle

Malignant hyperthermia (MH) is a life-threatening pharmacogenetic disorder triggered by volatile anaesthetics and depolarizing muscle relaxants. MH is characterized by excessive calcium release from the sarcoplasmic reticulum, often due to ryanodine receptor 1 (RYR1) mutations, leading to hypermetabolism, muscle rigidity and hyperthermia. While the RYR1 antagonist dantrolene remains the primary pharmacological treatment, its side effects necessitate exploration of alternative treatment options. Emerging evidence implicates the endocannabinoid system in muscle calcium homeostasis, suggesting its potential role in MH management. The endocannabinoid system comprises endogenous ligands (e.g. anandamide), cannabinoid receptors (e.g. cannabinoid receptor 1, CB1), and can modulate the calcium dynamics. CB1 activation inhibits PKA-mediated phosphorylation of RYR1 and L-type calcium channels, reducing myoplasmic calcium and muscle contractility, a mechanism that could counteract MH pathophysiology. In addition, antagonism or desensitization of the calcium channel transient receptor potential vanilloid 1 lowers calcium release from the sarcoplasmic reticulum. Preclinical studies demonstrate that CB1 agonism lowers body temperature and attenuates cardiovascular stress, aligning with MH therapeutic goals. This review synthesizes molecular insights linking endocannabinoid signaling to MH, highlighting its unexplored potential as an adjunctive therapy. Future research should validate these mechanisms in MH-specific models, including RYR1-mutant human myotubes, to translate ECS modulation into clinical practice.

恶性热疗（MH）是一种危及生命的药物遗传疾病，由挥发性麻醉剂和去极化肌肉松弛剂引发。MH的特点是肌浆网钙释放过多，通常是由于ryanodine受体1 （RYR1）突变，导致高代谢、肌肉僵硬和高热。虽然RYR1拮抗剂丹曲林仍然是主要的药物治疗，但其副作用需要探索替代治疗方案。新出现的证据暗示内源性大麻素系统参与肌肉钙稳态，提示其在MH管理中的潜在作用。内源性大麻素系统包括内源性配体（如大麻酰胺），大麻素受体（如大麻素受体1，CB1），并可以调节钙动力学。CB1激活抑制pka介导的RYR1磷酸化和l型钙通道，降低肌浆钙和肌肉收缩力，这一机制可能抵消MH病理生理。此外，钙通道瞬时受体电位香草样蛋白1的拮抗或脱敏降低了钙从肌浆网的释放。临床前研究表明，CB1激动剂可以降低体温，减轻心血管压力，符合MH的治疗目标。这篇综述综合了内源性大麻素信号与MH之间的分子联系，强调了其作为辅助治疗的未开发潜力。未来的研究应该在mh特异性模型中验证这些机制，包括ryr1突变的人肌管，以将ECS调节转化为临床实践。

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引用次数: 0

The balancing act between lipid droplets and lysosomes for membrane functionality in age-related neurodegeneration and inflammation 脂滴和溶酶体在年龄相关性神经变性和炎症中膜功能的平衡作用

IF 14 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Progress in lipid research

Pub Date : 2025-06-05 DOI: 10.1016/j.plipres.2025.101341

Mariana I. Tsap , Halyna R. Shcherbata

Age-related neurodegenerative disorders are often associated with disruptions in lipid metabolism. A critical aspect is the impairment of the interaction between lipid droplets (LDs) and lysosomal function, leading to the accumulation of toxic lipid species. This accumulation triggers cellular stress, inflammation, and defective waste processing within cells, disrupting cellular homeostasis and amplifying neuroinflammatory processes. Recent studies have shown that alterations in phospholipid and fatty acid homeostasis drive neuroinflammation and oxidative stress, exacerbating neurodegenerative processes. This review focuses on the role of neuropathy target esterase (PNPLA6/NTE) and NTE-related esterase (PNPLA7/NRE) in lipid metabolism, highlighting how dysregulation of these enzymes contributes to neurodegeneration, inflammation, and lysosomal dysfunction. Additionally, we discuss the involvement of lipid rafts, sphingolipids, and phospholipase enzymes, particularly PLA2 family members, in cellular signaling and membrane dynamics. By examining the relationship between lipid metabolism, inflammatory signaling, and lysosomal storage disorders, we aim to provide a comprehensive understanding of how LDs and lysosomes interact to influence cellular homeostasis in neurodegenerative conditions, which could lead to new therapeutic strategies addressing lipid dysregulation in age-related neurological disorders.

年龄相关性神经退行性疾病通常与脂质代谢紊乱有关。一个关键的方面是脂滴（ld）和溶酶体功能之间相互作用的损害，导致有毒脂质的积累。这种积累引发细胞应激、炎症和细胞内有缺陷的废物处理，破坏细胞稳态并放大神经炎症过程。最近的研究表明，磷脂和脂肪酸稳态的改变驱动神经炎症和氧化应激，加剧神经退行性过程。本文综述了神经病变靶酯酶（PNPLA6/NTE）和NTE相关酯酶（PNPLA7/NRE）在脂质代谢中的作用，强调了这些酶的失调如何导致神经变性、炎症和溶酶体功能障碍。此外，我们还讨论了脂筏、鞘脂和磷脂酶，特别是PLA2家族成员，在细胞信号传导和膜动力学中的作用。通过研究脂质代谢、炎症信号和溶酶体储存障碍之间的关系，我们旨在全面了解ld和溶酶体如何相互作用影响神经退行性疾病的细胞稳态，这可能会导致解决年龄相关神经疾病中脂质失调的新治疗策略。

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引用次数: 0