Biological Chemistry最新文献_第4页

Posttranslational modifications of RAS: few pockets but many bumps. RAS的翻译后修饰：少而多。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-04-17 Print Date: 2026-05-26 DOI: 10.1515/hsz-2026-0102

Mercedes Fissore-O'Leary, Mark Philips

引用次数: 0

Adherens junctions balance stability and motility: from cell morphogenesis to neural tissue patterning. 粘附连接平衡稳定性和运动性：从细胞形态发生到神经组织模式。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-04-08 Print Date: 2026-07-24 DOI: 10.1515/hsz-2025-0247

Joachim Fuchs, Kawtar Cherkaoui, P Robin Hiesinger

{"title":"Adherens junctions balance stability and motility: from cell morphogenesis to neural tissue patterning.","authors":"Joachim Fuchs, Kawtar Cherkaoui, P Robin Hiesinger","doi":"10.1515/hsz-2025-0247","DOIUrl":"10.1515/hsz-2025-0247","url":null,"abstract":"Adherens junctions are cellular contact sites that organize epithelial tissues and play well-characterized roles in the coordination of cell collectives. Intercellular contacts are mediated by cadherin- or nectin-based adhesion and intracellularly linked to the actin cytoskeleton via the molecular scaffolds catenin and afadin. In this review, we discuss the mechanisms and roles of these molecular scaffolds for cellular morphogenesis and collective cell behaviour with a focus on neural tissue patterning. We discuss the molecular mechanisms in the conceptual framework of two often opposing, but complementary demands on adherens junctions in developing neural tissues: stability through 'supracellular' cytoskeletal linkage across cells versus local, dynamically adhesive cellular interactions in morphogenesis. Molecular scaffolds mediate localization, mechanosensitive adhesion and the regulation of cytoskeleton tension in both mechanistic contexts. These complementary mechanisms allow for collective behaviour that has predominantly been characterized for the patterning of tissues consisting of cell bodies, but was recently shown to also underlie the patterning of an epithelial-like tissue made entirely of neuronal growth cones. Molecular scaffolding of adherens junctions thereby contributes to patterning mechanisms that may apply to diverse tissue types.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"235-245"},"PeriodicalIF":2.5,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The heart of the matter: a personal view of Fred Wittinghofer's contributions to RAS biology and drug design. 问题的核心：Fred Wittinghofer对RAS生物学和药物设计的贡献的个人观点。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-04-06 Print Date: 2026-05-26 DOI: 10.1515/hsz-2025-0244

Frank McCormick

引用次数: 0

Development of kallikrein-related peptidase 7 (KLK7) inhibitors and use in a species-adapted model for ovarian cancer. kallikrein相关肽酶7 （KLK7）抑制剂的开发及其在卵巢癌物种适应模型中的应用

IF 2.4 4区生物学

Biological Chemistry Pub Date : 2026-03-19 DOI: 10.1515/hsz-2025-0252

Torsten Steinmetzer, Laury S Mesa-Rangel, Sadaf Janghorban, Sajad Sabzi, Charlotte Boller, Alexander Maiwald, Heike Lang-Henkel, Sophia Bielesch, Julia Milisterfer, Giulia Magno, Holger Bronger, Dalila Darmoul, Viktor Magdolen, Tobias F Dreyer

{"title":"Development of kallikrein-related peptidase 7 (KLK7) inhibitors and use in a species-adapted model for ovarian cancer.","authors":"Torsten Steinmetzer, Laury S Mesa-Rangel, Sadaf Janghorban, Sajad Sabzi, Charlotte Boller, Alexander Maiwald, Heike Lang-Henkel, Sophia Bielesch, Julia Milisterfer, Giulia Magno, Holger Bronger, Dalila Darmoul, Viktor Magdolen, Tobias F Dreyer","doi":"10.1515/hsz-2025-0252","DOIUrl":"https://doi.org/10.1515/hsz-2025-0252","url":null,"abstract":"The serine protease KLK7 contributes to several skin disorders and tumorigenesis, making it an attractive drug target. Owing to structural similarities in the S1 binding pocket between human KLK7 and certain trypsin-like serine proteases harboring an Ala at position 190, compounds containing a chlorine-substituted benzylamide as P1 group were screened for KLK7 inhibition. Further optimization yielded the substrate analog inhibitor Bzls-d-hTyr-Pro-2-aminomethyl-5-chloro-benzylamide (K i value 29.3 nM), which, however, had insufficient selectivity against the tested clotting proteases. Guided by a published KLK7 crystal structure, a second, more selective non-peptide inhibitor series was synthesized. The best derivatives (K i values <100 nM) contain a chlorine-substituted aromatic P1 group and additionally address the non-prime region of KLK7. Murine Klk7 is poorly inhibited by these compounds; however, mutating threonine 190 in the S1 pocket to alanine restored the inhibitory potency. The new inhibitors effectively block KLK7-mediated functions, including chemokine cleavage and moesin gene upregulation, without cytotoxicity towards murine ovarian cancer cells. Moreover, tumors derived from ovarian cancer cells overexpressing either wild-type or mutated Klk7 reduced overall survival in mice compared to vector control cells. Together, these findings establish a robust inhibitor-enzyme system to evaluate human KLK7 inhibitors in a preclinical mouse model.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of Aβ(40) peptide aggregation by Milk-derived Amyloid-like Protein Aggregates (MAPA). 乳源性淀粉样蛋白聚集体（MAPA）对Aβ(40)肽聚集的抑制作用

IF 2.4 4区生物学

Biological Chemistry Pub Date : 2026-03-19 DOI: 10.1515/hsz-2025-0208

Shweta Malik, Indranil De, Abhishek Singh Yadav, Vikash Poonia, Kritika Gaur, Pankaj Goyal, Manish Singh, Jay Kant Yadav

{"title":"Inhibition of Aβ(40) peptide aggregation by Milk-derived Amyloid-like Protein Aggregates (MAPA).","authors":"Shweta Malik, Indranil De, Abhishek Singh Yadav, Vikash Poonia, Kritika Gaur, Pankaj Goyal, Manish Singh, Jay Kant Yadav","doi":"10.1515/hsz-2025-0208","DOIUrl":"https://doi.org/10.1515/hsz-2025-0208","url":null,"abstract":"Recent studies have identified Aβ peptides in human gut epithelial cells, along with several amyloid-forming proteins and peptides in the gut lumen. These findings suggest that Aβ or other amyloid-like molecules originating from the gut may contribute to the involvement of the gastrointestinal system in the development of Alzheimer's disease (AD) pathology. Modulating the aggregation behaviour of Aβ and other amyloid forming peptides/proteins present in the gut may represent novel strategy to mitigate AD pathology. This study explores the use of Milk-derived Amyloid-like Protein Aggregates (MAPA) to inhibit Aβ(40) aggregation in vitro. MAPA's inhibitory effects were assessed using amyloid dye-binding assays (Thioflavin T, Congo Red, and ANS) and transmission electron microscopy. Toxicity assays showed that the MAPA significantly reduced Aβ(40)-induced neuronal death. Fluorescence quenching suggest MAPA physically interacts with Aβ(40) to prevent its aggregation. By blocking Aβ aggregation and reducing its neurotoxicity, MAPA presents a promising organic strategy to counteract AD progression influenced by gut factors. These findings open new avenues for AD prevention and the disease management, especially via dietary interventions targeting the gastro-intestinal system.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147479665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Albrecht Kossel and the nucleobases - a review of his life and work. 阿尔布雷希特·科塞尔和核碱基——回顾他的生活和工作。

IF 2.4 4区生物学

Biological Chemistry Pub Date : 2026-02-27 DOI: 10.1515/hsz-2026-0107

Edith Framm, Joachim Framm

引用次数: 0

CCM scaffolds at the frontier of biomechanics: their roles in vascular physiology and disease. 生物力学前沿的CCM支架：它们在血管生理和疾病中的作用。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-02-25 Print Date: 2026-07-24 DOI: 10.1515/hsz-2025-0246

Claudia Jasmin Rödel, Salim Abdelilah-Seyfried

{"title":"CCM scaffolds at the frontier of biomechanics: their roles in vascular physiology and disease.","authors":"Claudia Jasmin Rödel, Salim Abdelilah-Seyfried","doi":"10.1515/hsz-2025-0246","DOIUrl":"https://doi.org/10.1515/hsz-2025-0246","url":null,"abstract":"Cerebral cavernous malformation (CCM) is a genetic vascular disorder arising from endothelial dysfunction, affecting the microvasculature of the central nervous system. Patients with mutations in any of three CCM genes may suffer from neurological deficits and even hemorrhagic stroke. The three CCM proteins are structurally unrelated and assemble into the CCM complex that forms scaffolds associated with junctional complexes and the actomyosin cytoskeleton. Recent work points to a dual role of the CCM complex in structural scaffolding and mechanosensitive signal transduction. In this review, we highlight recent advances examining the CCM complex's role in organizing various multi-protein interactions and facilitating mechanosensitive signaling that regulates endothelial cell behavior. Importantly, accumulating evidence emphasizes the impact of hemodynamic forces on CCM signaling, pointing to distinct mechanisms in arterial versus venous vessels. Surprisingly, the loss of CCM proteins has vasoprotective effects in arteries but pathological effects in veins and small capillaries. Understanding CCM scaffolds that integrate structural support with mechanosensitive signaling is fundamental to deciphering the molecular mechanisms that underlie physiological versus pathological outcomes within the vasculature. This knowledge advances the development of targeted therapeutic strategies aimed at restoring endothelial integrity and normal vascular function, particularly by modulating signaling pathways influenced by hemodynamic forces.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":"407 4-6","pages":"247-258"},"PeriodicalIF":2.5,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Endocytic scaffolds at the crossroads of Alzheimer's disease and neuronal aging. 内吞支架在阿尔茨海默病和神经元老化的十字路口。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-02-13 Print Date: 2026-07-24 DOI: 10.1515/hsz-2025-0250

Jasmeet Kaur Shergill, Domenico Azarnia Tehran

{"title":"Endocytic scaffolds at the crossroads of Alzheimer's disease and neuronal aging.","authors":"Jasmeet Kaur Shergill, Domenico Azarnia Tehran","doi":"10.1515/hsz-2025-0250","DOIUrl":"10.1515/hsz-2025-0250","url":null,"abstract":"More than a century after Alois Alzheimer's neuropathological description, the mechanisms driving Alzheimer's disease (AD) remain only partially understood, and the failure of most clinical trials underscores the need to identify and target alternative pathogenic pathways. Recent genetic, biochemical, and cellular studies support the view that AD is characterized by early alterations in the endolysosomal system and implicate multiple endocytic scaffold proteins as key drivers of AD progression. In this review, we summarize the current knowledge of five endocytic scaffold proteins, CALM, AP-2, BIN1, CD2AP, and ITSN1, which have been identified as AD risk factors by genome-wide association studies. We describe how, under physiological conditions, they couple membrane remodeling to intracellular signaling, whereas in AD they influence amyloid precursor protein trafficking, amyloid-β (Aβ) generation, tau pathology, and synaptic integrity. Finally, we propose a model in which cell type-specific and age-dependent dysfunction of endocytic scaffolds defines a pathogenic hotspot of proteostasis failure and offers new entry points for therapeutic intervention.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"185-197"},"PeriodicalIF":2.5,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146199851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intersectins as versatile scaffolds for membrane-associated processes. 交叉点作为膜相关过程的多功能支架。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-01-20 Print Date: 2026-07-24 DOI: 10.1515/hsz-2025-0228

Alexandra Hilse, Tanja Maritzen

引用次数: 0

Getting to the right place at the right time - membrane trafficking and maturation in the endolysosomal system. 在正确的时间到达正确的地点-内溶酶体系统的膜运输和成熟。

IF 2.4 4区生物学

Biological Chemistry Pub Date : 2025-12-29 Print Date: 2025-12-17 DOI: 10.1515/hsz-2025-0187

Alexander Stockhammer, Christian Ungermann

引用次数: 0