Molecular Aspects of Medicine最新文献_第5页

Cardiovascular impact of emerging and Re-emerging Viruses: Pathophysiological mechanisms, diagnosis, and management with a pediatric focus 新出现的和再出现的病毒对心血管的影响：病理生理机制、诊断和管理，以儿科为重点

IF 8.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-08-01 Epub Date: 2025-05-26 DOI: 10.1016/j.mam.2025.101371

Li Li , Xu Shi , Ruiming Wang , Yuxi Fan , Zhihan Xu , Habibollah Mirzaei , Wuran Wei

Emerging and re-emerging viruses are currently known as a major public health issue. These viruses can cause various human complications such as cardiovascular diseases (CVDs), both in adults and pediatric populations. Although various CVDs have been previously reported for emerging and re-emerging viruses, the mechanisms underlying these complications remain relatively unknown. Children and infants, while commonly developing less severe symptoms, may experience notable cardiovascular manifestations during infections caused by emerging and re-emerging viral infections, which can result in both acute and long-term complications. The present review aims to discuss various cardiovascular complications linked to emerging and re-emerging viral pathogens (including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV)) such as arrhythmias, myocarditis, vascular disorders, and thromboembolic conditions, particularly among the pediatric population. This review also addresses the potential mechanisms by which SARS-CoV-2, DENV, ZIKV, and CHIKV may impact the cardiovascular system and their clinical implications. Moreover, it discusses the diagnostic challenges for viral-caused cardiovascular disorders in children, owing to their common subtle or atypical manifestations. Finally, it addresses the present therapeutic specifically used for pediatric cases.

新出现和再出现的病毒目前被认为是一个重大的公共卫生问题。这些病毒可在成人和儿童人群中引起各种人类并发症，如心血管疾病（cvd）。虽然以前已经报道了新出现和再出现的病毒引起的各种心血管疾病，但这些并发症的机制仍然相对未知。儿童和婴儿虽然通常出现不太严重的症状，但在新发和再发病毒感染引起的感染期间可能出现明显的心血管症状，这可能导致急性和长期并发症。本综述旨在讨论与新出现和再出现的病毒性病原体（包括严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）、登革热病毒（DENV）、寨卡病毒（ZIKV）和基孔肯雅病毒（CHIKV））相关的各种心血管并发症，如心律失常、心肌炎、血管疾病和血栓栓塞性疾病，特别是在儿科人群中。本综述还探讨了SARS-CoV-2、DENV、ZIKV和CHIKV可能影响心血管系统的潜在机制及其临床意义。此外，它讨论了诊断挑战的病毒引起的心血管疾病的儿童，由于他们的共同微妙或非典型的表现。最后，它解决了目前治疗专门用于儿科病例。

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引用次数: 0

Protein and RNA chaperones 蛋白质和RNA伴侣

IF 8.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-08-01 Epub Date: 2025-07-14 DOI: 10.1016/j.mam.2025.101384

Bikash R. Sahoo, James CA. Bardwell

Cells preserve macromolecular homeostasis by utilizing molecular chaperones that prevent aggregation or promote correct folding of protein and RNA. Here we discuss non-traditional proteinaceous chaperones like RNA-binding chaperones that work by modulating RNA structure, preventing aberrant interactions, and regulating intracellular granule dynamics. We also discuss the chaperone functions of other macromolecules such as nucleic acids, and in particular G-quadruplexes, which are very effective at preventing protein aggregation and accelerating protein folding. These chaperones are particularly important in G-quadruplex linked amyloid aggregation and repeat-expansion diseases such as Parkinson's disease and amyotrophic lateral sclerosis, where RNA aggregation and misfolded protein accumulation co-occur. By comparing protein and non-protein chaperone systems, we highlight the principles that underlie chaperone action across molecular classes.

细胞通过利用分子伴侣来防止蛋白质和RNA的聚集或促进正确折叠，从而保持大分子的稳态。在这里，我们讨论非传统的蛋白质伴侣，如RNA结合伴侣，通过调节RNA结构，防止异常相互作用和调节细胞内颗粒动力学起作用。我们还讨论了其他大分子的伴侣功能，如核酸，特别是g -四联体，它在防止蛋白质聚集和加速蛋白质折叠方面非常有效。这些伴侣蛋白在g -四重体相关淀粉样蛋白聚集和重复扩张疾病（如帕金森病和肌萎缩侧索硬化症）中尤为重要，在这些疾病中，RNA聚集和错误折叠的蛋白质积累共同发生。通过比较蛋白质和非蛋白质伴侣系统，我们强调了在分子类中伴侣作用的原理。

引用次数: 0

Ischemia - Reperfusion injury: A roadmap to precision therapies 缺血-再灌注损伤：精确治疗的路线图

IF 8.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-08-01 Epub Date: 2025-07-08 DOI: 10.1016/j.mam.2025.101382

Wei Li , Yan Liao , Jie Chen , Weichao Kang , Xintao Wang , Xiaozhu Zhai , Ying Xue , Wangzheqi Zhang , Yiyang Xia , Derong Cui

Ischemia-reperfusion (I/R) injury is prevalent in the medical field and significantly limits the therapeutic outcomes of various ischemic diseases, adversely affecting patient prognosis. The pathogenesis of I/R injury is highly complex, involving intricate interactions among oxidative stress, inflammatory responses, mitochondrial dysfunction, and multiple cell death pathways. Once the mitochondrial respiratory chain is impaired, it triggers oxidative stress responses, leading to the excessive production of reactive oxygen species (ROS). Excessive ROS not only directly damage cells but also activate inflammatory responses and initiate multiple cell death signalling pathways, such as necroptosis, pyroptosis, and ferroptosis, thereby exacerbating tissue damage. Moreover, the clinical manifestations of I/R injury vary significantly across different organs, such as the heart, brain, kidneys, liver, and lungs, and are further influenced by patients' underlying conditions, posing challenges for clinical diagnosis and treatment. Therefore, constructing a comprehensive assessment system based on individual patient characteristics (such as genetic polymorphisms and comorbidities) to accurately predict the risk of I/R injury is particularly important. Currently, there are diverse strategies for the prevention and treatment of I/R injury, but translating basic research into clinical application remains challenging. Developing personalized treatment plans tailored to different cell types holds promise for overcoming existing therapeutic bottlenecks, significantly improving patient outcomes, and providing new directions for addressing the challenges of I/R injury.

缺血再灌注（I/R）损伤在医学领域普遍存在，严重限制了各种缺血性疾病的治疗效果，对患者预后产生不利影响。I/R损伤的发病机制非常复杂，涉及氧化应激、炎症反应、线粒体功能障碍和多种细胞死亡途径之间复杂的相互作用。一旦线粒体呼吸链受损，就会引发氧化应激反应，导致活性氧（ROS）的过量产生。过多的ROS不仅会直接损伤细胞，还会激活炎症反应，启动多种细胞死亡信号通路，如坏死、焦亡、铁亡等，从而加重组织损伤。此外，I/R损伤的临床表现在心、脑、肾、肝、肺等不同器官之间存在显著差异，并进一步受到患者基础疾病的影响，给临床诊断和治疗带来挑战。因此，构建基于患者个体特征（如遗传多态性、合并症等）的综合评估体系，准确预测I/R损伤风险就显得尤为重要。目前，预防和治疗I/R损伤的策略多种多样，但将基础研究转化为临床应用仍然具有挑战性。开发针对不同细胞类型的个性化治疗方案有望克服现有的治疗瓶颈，显著改善患者的预后，并为解决I/R损伤的挑战提供新的方向。

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引用次数: 0

Respiratory emerging viruses and drug resistance in lung cancer: challenges and new perspectives in treatment 呼吸道新发病毒和肺癌的耐药：治疗的挑战和新观点

IF 8.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-08-01 Epub Date: 2025-07-15 DOI: 10.1016/j.mam.2025.101383

Qiang Wu , Wen Li , Hongli Liu , Yinyin Xue , Kaili Huang , Hossein Pourghadamyari , Zhenkun Liu

Emerging viral pathogens, particularly those targeting the respiratory system such as SARS-CoV-2 and influenza virus, pose significant challenges for patients with lung cancer. These patients show increased susceptibility to serious infections caused by these viruses as a result of immunosuppression from various therapies such as immunotherapy, chemotherapy, and targeted agents. Respiratory viral infections can induce tumor progression and drug resistance through affecting the tumor microenvironment (TME), modulating immune checkpoints, or interfering with therapeutic efficacy. The present review discusses the reciprocal interactions between these viral pathogens and lung cancer, underscoring mechanisms by which SARS-CoV-2 and influenza viruses affect the lung cancer TME promoting tumor progression, immune evasion, and ultimately, resistance to anti-cancer therapies such as tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). Sections discussed in this study include: (i) increased susceptibility to viral infections, (ii) virus-induced modulation of the tumor microenvironment, and (iii) mechanisms of therapy resistance. This review also addresses emerging strategies, such as oncolytic virotherapy, as potential candidates for lung cancer treatment. It aims to provide new perspectives on therapeutic optimization for patients with lung cancer in the context of SARS-CoV-2 and influenza viruses, by reviewing evidence from virology, oncology, and immunology.

新出现的病毒病原体，特别是针对呼吸系统的病毒，如SARS-CoV-2和流感病毒，给肺癌患者带来了重大挑战。由于免疫疗法、化疗和靶向药物等各种疗法的免疫抑制，这些患者对这些病毒引起的严重感染的易感性增加。呼吸道病毒感染可通过影响肿瘤微环境（TME）、调节免疫检查点或干扰治疗效果诱导肿瘤进展和耐药。本综述讨论了这些病毒病原体与肺癌之间的相互作用，强调了SARS-CoV-2和流感病毒影响肺癌TME促进肿瘤进展、免疫逃避并最终对酪氨酸激酶抑制剂（TKIs）和免疫检查点抑制剂（ICIs）等抗癌疗法产生耐药性的机制。本研究中讨论的部分包括：(1)对病毒感染的易感性增加，(2)病毒诱导的肿瘤微环境调节，以及(3)耐药机制。本综述还讨论了新兴策略，如溶瘤病毒治疗，作为肺癌治疗的潜在候选。本研究旨在通过回顾病毒学、肿瘤学和免疫学方面的证据，为SARS-CoV-2和流感病毒背景下肺癌患者的治疗优化提供新的视角。

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引用次数: 0

Type 2 Diabetes Mellitus and bladder cancer: A narrative review on associated signaling pathways 2型糖尿病和膀胱癌：相关信号通路的叙述综述

IF 8.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-08-01 Epub Date: 2025-06-20 DOI: 10.1016/j.mam.2025.101381

Lívia da Cunha Agostini, Glenda Nicioli da Silva

Bladder cancer is one of the most common cancers globally. The risk factors for urothelial bladder cancer can be broadly divided into genetic predispositions and external environmental exposures. Type 2 Diabetes Mellitus (T2DM) is a chronic, non-communicable metabolic disorder, and the interaction between genetic, behavioral, and environmental factors plays a significant role in its development. The management of T2DM includes lifestyle modifications and medication. Several studies suggest that T2DM is associated with an increased risk of bladder cancer. This review highlights the key signaling mechanisms involved in this association and explores the impact of T2DM medications on bladder cancer. In conclusion, the literature suggests that metabolic abnormalities associated with T2DM —such as hyperglycemia, insulin resistance and elevated levels of insulin, insulin-like growth factor 1 (IGF-1), inflammatory cytokines, iNOS/eNOS activity, hypoxia, dyslipidemia, matrix metalloproteinase (MMPs), leptin, vimentin, N-cadherin, fibronectin, advanced glycation end products (AGEs), endoplasmic reticulum stress (ERS), and Arntl2 gene expression; in addition to reduced E-cadherin, adiponectin, autophagy, and IGF-1 and Usp2 gene expression—significantly influence signaling pathways essential for bladder tumor development. Additionally, the choice of hypoglycemic treatment should be carefully considered, taking into account potential effects on carcinogenesis.

膀胱癌是全球最常见的癌症之一。尿路上皮性膀胱癌的危险因素大致可分为遗传易感性和外部环境暴露。2型糖尿病（T2DM）是一种慢性非传染性代谢性疾病，遗传、行为和环境因素的相互作用在其发病过程中起着重要作用。T2DM的管理包括生活方式的改变和药物治疗。一些研究表明，2型糖尿病与膀胱癌风险增加有关。这篇综述强调了这种关联的关键信号机制，并探讨了T2DM药物对膀胱癌的影响。总之，文献提示与T2DM相关的代谢异常，如高血糖、胰岛素抵抗和胰岛素水平升高、胰岛素样生长因子1 （IGF-1）、炎症因子、iNOS/eNOS活性、缺氧、血脂异常、基质金属蛋白酶（MMPs）、瘦素、vimentin、n-钙粘蛋白、纤维连接蛋白、晚期糖基化终产物（AGEs）、内质网应激（ERS）和Arntl2基因表达；除了e -钙粘蛋白、脂联素、自噬、IGF-1和Usp2基因表达减少外，还显著影响膀胱肿瘤发展所必需的信号通路。此外，应仔细考虑降糖治疗的选择，考虑到潜在的致癌作用。

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引用次数: 0

Invasive fungal infections: An expanding and evolving threat 侵袭性真菌感染：一种不断扩大和演变的威胁。

IF 10.3 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-08-01 Epub Date: 2025-04-29 DOI: 10.1016/j.mam.2025.101363

Matteo Bassetti , Antonio Vena

引用次数: 0

The role of free fatty acid receptors activation in pancreatic disorders 游离脂肪酸受体激活在胰腺疾病中的作用

IF 8.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-08-01 Epub Date: 2025-07-12 DOI: 10.1016/j.mam.2025.101386

Julia Lis, Jakub Fichna, Aleksandra Tarasiuk-Zawadzka

Free fatty acid receptors (FFARs), a subset of G protein-coupled receptors, play a pivotal role in metabolic and immune homeostasis by modulating signaling pathways in response to free fatty acids. The four main FFARs (FFAR1, FFAR2, FFAR3, and FFAR4) are especially significant in pancreatic function, regulating insulin secretion, inflammation, and glucose metabolism. These receptors are involved in key pancreatic disorders, including acute pancreatitis (AP), pancreatic cancer (PC), type 1 diabetes (T1D), and type 2 diabetes (T2D).

FFAR1, FFAR3, and FFAR4 exhibit protective effects against AP due to their anti-inflammatory properties. In PC, FFAR1 inhibits tumor cell motility, while FFAR2 downregulation may contribute to tumor progression. FFAR3 plays a role in limiting tumor proliferation, whereas FFAR4 has a dual effect, promoting metastasis while also triggering tumor cell apoptosis. In T1D, FFAR2 and FFAR4 help regulate glycemia without directly stimulating insulin secretion. In T2D, all four FFARs contribute to glycemic control and may protect pancreatic β-cells.

Despite their therapeutic potential, the precise mechanisms underlying FFAR function in pancreatic disorders remain incompletely understood. Ongoing research aims to clarify these pathways, identify optimal ligands, and assess the safety and efficacy of FFAR-targeted therapies. This growing body of evidence underscores the importance of FFARs as potential targets for innovative treatments in pancreatic diseases.

游离脂肪酸受体（FFARs）是G蛋白偶联受体的一个子集，通过调节游离脂肪酸应答的信号通路，在代谢和免疫稳态中发挥关键作用。四种主要FFARs （FFAR1、FFAR2、FFAR3和FFAR4）在胰腺功能、调节胰岛素分泌、炎症和葡萄糖代谢中尤为重要。这些受体参与关键胰腺疾病，包括急性胰腺炎（AP）、胰腺癌（PC）、1型糖尿病（T1D）和2型糖尿病（T2D）。FFAR1、FFAR3和FFAR4由于其抗炎特性对AP表现出保护作用。在PC中，FFAR1抑制肿瘤细胞运动，而FFAR2下调可能促进肿瘤进展。FFAR3发挥限制肿瘤增殖的作用，而FFAR4具有双重作用，既促进肿瘤转移，又触发肿瘤细胞凋亡。在T1D中，FFAR2和FFAR4在不直接刺激胰岛素分泌的情况下帮助调节血糖。在T2D中，所有四种ffar都有助于血糖控制，并可能保护胰腺β细胞。尽管具有治疗潜力，但FFAR在胰腺疾病中功能的确切机制仍不完全清楚。正在进行的研究旨在阐明这些途径，确定最佳配体，并评估ffar靶向治疗的安全性和有效性。越来越多的证据强调了FFARs作为胰腺疾病创新治疗的潜在靶点的重要性。

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引用次数: 0

Duration of systemic antifungal therapy for patients with invasive fungal diseases: A reassessment 侵袭性真菌疾病患者全身抗真菌治疗的持续时间：再评估

IF 8.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-06-01 Epub Date: 2025-03-14 DOI: 10.1016/j.mam.2025.101347

Simon B. Gressens , Claire Rouzaud , Frederic Lamoth , Thierry Calandra , Fanny Lanternier , Olivier Lortholary

Invasive fungal diseases are associated with significant morbidity and mortality, especially among immunocompromised patients, and often prompt for rapid and aggressive treatment aiming cure. Due to the expanding magnitude of patients burdened by chronic immunosuppression and affected by fungal diseases, the diversity of clinical settings has risen. This often results in prolonged therapy (induction, consolidation and maintenance) associated with potentially severe side effects, and clinicians face the challenging decisions of when and how to stop anti-fungal therapy. Adequate duration of therapy is poorly defined, hampered by the lack of dedicated trials to the question, the heterogeneity of cases (type of fungal pathogen, localization of infection, underlying host conditions) and various confounding factors that may influence the clinical response (e.g. persistence vs recovery of immunosuppression, impact of surgery). In this review, we aim to evaluate the existing data underlying the guidelines and recommendations of treatment duration for the most frequent invasive fungal diseases (cryptococcal meningitis, Pneumocystis pneumonia, invasive aspergillosis, invasive candidiasis and mucormycosis), as well as specific localizations of deep-seated diseases (osteo-articular or central nervous system diseases and endocarditis) and emerging considerations and strategies.

侵袭性真菌疾病与显著的发病率和死亡率相关，特别是在免疫功能低下的患者中，通常需要快速和积极的治疗以治愈。由于受慢性免疫抑制和真菌疾病影响的患者数量不断增加，临床环境的多样性也在增加。这通常导致治疗时间延长（诱导、巩固和维持），并伴有潜在的严重副作用，临床医生面临着何时以及如何停止抗真菌治疗的挑战性决定。由于缺乏针对该问题的专门试验、病例的异质性（真菌病原体的类型、感染的定位、潜在的宿主条件）以及可能影响临床反应的各种混杂因素（例如免疫抑制的持续与恢复、手术的影响），对适当的治疗持续时间的定义不明确。在这篇综述中，我们旨在评估最常见的侵袭性真菌疾病（隐球菌性脑膜炎、肺囊虫性肺炎、侵袭性曲霉病、侵袭性念珠菌病和毛霉病）的治疗时间指南和建议的现有数据，以及深层疾病（骨关节或中枢神经系统疾病和心内膜炎）的特定定位以及新出现的考虑和策略。

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引用次数: 0

Virus-like particles of retroviral origin in protein aggregation and neurodegenerative diseases 蛋白质聚集和神经退行性疾病中源自逆转录病毒的病毒样颗粒

IF 8.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-06-01 Epub Date: 2025-05-20 DOI: 10.1016/j.mam.2025.101369

Serena Carra , Balazs Fabian , Hamed Taghavi , Edoardo Milanetti , Valeria Giliberti , Giancarlo Ruocco , Jason Shepherd , Michele Vendruscolo , Monika Fuxreiter

A wide range of human diseases are associated with protein misfolding and amyloid aggregates. Recent studies suggest that in certain neurological disorders, including Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD) and various tauopathies, protein aggregation may be promoted by virus-like particles (VLPs) formed by endogenous retroviruses (ERVs). The molecular mechanisms by which these VLPs contribute to protein aggregation, however, remain enigmatic. Here, we discuss possible molecular mechanisms of ERV-derived VLPs in the formation and spread of protein aggregates. An intriguing possibility is that liquid-like condensates may facilitate the formation of both protein aggregates and ERV-derived VLPs. We also describe how RNA chaperoning, and the encapsulation and trafficking of misfolded proteins, may contribute to protein homeostasis through the elimination of protein aggregates from cells. Based on these insights, we discuss future potential therapeutic opportunities.

许多人类疾病都与蛋白质错误折叠和淀粉样蛋白聚集有关。最近的研究表明，在某些神经系统疾病中，包括肌萎缩侧索硬化症（ALS）、额颞叶痴呆（FTD）和各种牛头病，内源性逆转录病毒（erv）形成的病毒样颗粒（vlp）可能促进蛋白质聚集。然而，这些VLPs促进蛋白质聚集的分子机制仍然是谜。在这里，我们讨论了erv衍生的VLPs在蛋白质聚集体形成和扩散中的可能分子机制。一种有趣的可能性是，液体状凝聚物可能促进蛋白质聚集体和erv衍生的VLPs的形成。我们还描述了RNA陪伴，以及错误折叠蛋白质的封装和运输，如何通过消除细胞中的蛋白质聚集体来促进蛋白质稳态。基于这些见解，我们讨论了未来潜在的治疗机会。

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引用次数: 0

The thermodynamic hypothesis of protein aggregation 蛋白质聚集的热力学假设

IF 8.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-06-01 Epub Date: 2025-05-03 DOI: 10.1016/j.mam.2025.101364

Michele Vendruscolo

Protein misfolding and aggregation drive some of the most prevalent and lethal disorders of our time, including Alzheimer's and Parkinson's diseases, now affecting tens of millions of people worldwide. The complexity of these diseases, which are often multifactorial and related to age and lifestyle, has made it challenging to identify the causes of the accumulation of aberrant protein deposits. An insight into the origins of these deposits comes from reports of a widespread presence of protein aggregates even under normal cellular conditions. This observation is best accounted for by the thermodynamic hypothesis of protein aggregation. According to this hypothesis, many proteins are expressed at levels close to their supersaturation limits, so that their native states are metastable against aggregation. Here we integrate the evidence behind this hypothesis and outline actionable therapeutic strategies that could halt protein aggregation at its source.

蛋白质错误折叠和聚集导致了我们这个时代一些最普遍和最致命的疾病，包括阿尔茨海默病和帕金森病，目前影响着全世界数千万人。这些疾病往往是多因素的，与年龄和生活方式有关，其复杂性使得确定异常蛋白质沉积积累的原因具有挑战性。对这些沉积物起源的深入了解来自于蛋白质聚集体广泛存在的报道，甚至在正常的细胞条件下。这一观察结果最好用蛋白质聚集的热力学假设来解释。根据这一假设，许多蛋白质在接近其过饱和极限的水平上表达，因此它们的天然状态是亚稳态的。在这里，我们整合了这一假设背后的证据，并概述了可行的治疗策略，可以在源头上阻止蛋白质聚集。

引用次数: 0