Enzymes最新文献_第2页

Enzymes Pub Date : 2026-01-01 Epub Date: 2026-05-28 DOI: 10.1016/bs.enz.2026.05.003

Tashnuva Rifat, Mathias Sanchez Machado, Marc A Ilies

引用次数: 0

Matrix metalloproteinases (MMPs) in neurodegenerative diseases, an updated overview of the role of MT1-MMP and MT5-MMP in Alzheimer's disease. 神经退行性疾病中的基质金属蛋白酶（MMPs）， MT1-MMP和MT5-MMP在阿尔茨海默病中的作用的最新概述。

Enzymes Pub Date : 2026-01-01 Epub Date: 2026-08-14 DOI: 10.1016/bs.enz.2026.07.004

Marielle Frank, Cyrille Barthélémy, Antoine Dufour, Santiago Rivera, Kévin Baranger

{"title":"Matrix metalloproteinases (MMPs) in neurodegenerative diseases, an updated overview of the role of MT1-MMP and MT5-MMP in Alzheimer's disease.","authors":"Marielle Frank, Cyrille Barthélémy, Antoine Dufour, Santiago Rivera, Kévin Baranger","doi":"10.1016/bs.enz.2026.07.004","DOIUrl":"https://doi.org/10.1016/bs.enz.2026.07.004","url":null,"abstract":"Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Huntington's disease, pose an increasing threat to global health due to ageing populations and the lack of effective treatments. Matrix metalloproteinases (MMPs), which are proteases that belong to the metzincin superfamily, are critical regulators of neuroinflammation, blood-brain barrier integrity, protein misfolding, synaptic dysfunction and neuronal death. This chapter provides a comprehensive overview of the roles of MMPs at the intersection of the molecular and cellular mechanisms that underpin neurodegenerative processes. The focus is on their pathophysiological mechanisms, therapeutic potential, and recent advances. We highlight novel mechanistic insights in Alzheimer's disease, such as the roles of MT1-MMP and MT5-MMP in amyloid-beta peptide production and the dual functions of MMPs in both neuroprotection and neurotoxicity. This review emphasizes the need for further mechanistic research into the different MMPs involved in neurodegenerative diseases.","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"60 ","pages":"209-241"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149026312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Carbonic anhydrase III. 碳酸酐酶III。

Enzymes Pub Date : 2026-01-01 Epub Date: 2026-06-19 DOI: 10.1016/bs.enz.2026.05.007

Alessio Nocentini

引用次数: 0

Carbonic anhydrase VII: Development of selective inhibitors and their pharmacological significance. 碳酸酐酶VII：选择性抑制剂的发展及其药理意义。

Enzymes Pub Date : 2026-01-01 Epub Date: 2026-06-25 DOI: 10.1016/bs.enz.2026.05.008

Chandra Bhushan Mishra, Claudiu T Supuran

{"title":"Carbonic anhydrase VII: Development of selective inhibitors and their pharmacological significance.","authors":"Chandra Bhushan Mishra, Claudiu T Supuran","doi":"10.1016/bs.enz.2026.05.008","DOIUrl":"https://doi.org/10.1016/bs.enz.2026.05.008","url":null,"abstract":"Human carbonic anhydrase VII (hCA VII) is a cytosolic zinc metalloenzyme largely expressed in the brain, where it plays an important role in regulating intracellular pH. hCA VII emerged as a valuable therapeutic target for epilepsy and other neurological disorders due to its involvement in neuronal excitability and seizure generation. We provide a comprehensive outline of the structural features, physiological functions, and pathological significance of hCA VII. Recent advances in medicinal chemistry research, aimed at developing selective hCA VII inhibitors, are discussed in detail, including drug design strategy, structure-activity relationship, and inhibitory activity. Numerous classes of compounds, such as sulfonamides, sulfamides, and various heterocyclic scaffolds, have been widely used to develop effective and selective hCA VII inhibitors. The pharmacological actions of the developed hCA VII inhibitors, including antiepileptic, neuroprotective, and other neurological effects, are also discussed in detail, together with hCA VII activators. Overall, we highlight the therapeutic potential of hCA VII as a target for treating several neurological disorders, including epilepsy, providing valuable guidance for the future design of therapeutic molecules targeting it.","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"59 ","pages":"155-175"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148563276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial carbonic anhydrases VA and VB: Metabolic roles and clinical significance. 线粒体碳酸酐酶VA和VB的代谢作用及临床意义。

Enzymes Pub Date : 2026-01-01 Epub Date: 2026-05-27 DOI: 10.1016/bs.enz.2026.05.002

Stanislav Kalinin, Seppo Parkkila, Ashok Aspatwar

{"title":"Mitochondrial carbonic anhydrases VA and VB: Metabolic roles and clinical significance.","authors":"Stanislav Kalinin, Seppo Parkkila, Ashok Aspatwar","doi":"10.1016/bs.enz.2026.05.002","DOIUrl":"https://doi.org/10.1016/bs.enz.2026.05.002","url":null,"abstract":"Mitochondrial carbonic anhydrases VA and VB (CA VA and CA VB) are localized within the mitochondrial matrix. These zinc-containing enzymes catalyze the reversible hydration of carbon dioxide to bicarbonate and protons, thereby providing bicarbonate for essential mitochondrial metabolic reactions and contributing to intracellular pH balance. CA VA is predominantly expressed in the liver and plays a key role in supplying bicarbonate for pathways such as gluconeogenesis, ureagenesis, and lipogenesis. In contrast, CA VB shows a broader tissue distribution and supports mitochondrial metabolism across multiple organs, although its physiological role is less clearly defined. Mitochondrial CAs are directly linked to metabolic processes required for energy homeostasis. Deficiency of CA VA is associated with metabolic disorders, particularly those involving impaired ammonia detoxification and disruption of intermediary metabolism. This chapter summarizes current knowledge on CA VA and CA VB, including their molecular and structural features, biochemical properties, tissue distribution, and roles in mitochondrial metabolism. In addition, evidence from experimental models, clinical findings related to CA5A mutations, and emerging therapeutic perspectives are discussed.","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"59 ","pages":"105-130"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148563292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phylogenetic relationship of vertebrate carbonic anhydrases. 脊椎动物碳酸酐酶的系统发育关系。

Enzymes Pub Date : 2026-01-01 Epub Date: 2026-03-25 DOI: 10.1016/bs.enz.2026.03.002

Claudiu T Supuran, Clemente Capasso

{"title":"Phylogenetic relationship of vertebrate carbonic anhydrases.","authors":"Claudiu T Supuran, Clemente Capasso","doi":"10.1016/bs.enz.2026.03.002","DOIUrl":"10.1016/bs.enz.2026.03.002","url":null,"abstract":"Carbonic anhydrases (CAs, EC 4.2.1.1) are zinc-dependent metalloenzymes that catalyze the reversible hydration of carbon dioxide, a reaction essential for acid-base regulation, respiration, and metabolic integration in vertebrates. In animals, CA activity is exclusively encoded by the α-CA family, which has undergone extensive expansion during vertebrate evolution. This chapter presents a phylogenetic synthesis of vertebrate α-CAs, integrating sequence-based analyses with comparative genomics, structural constraints, and patterns of subcellular localization. Phylogenetic evidence indicates that the modern vertebrate CA repertoire originated early in the evolution of life, and was shaped by ancient whole-genome duplication events, followed by differential retention, divergence, and lineage-specific gene loss. Cytosolic, mitochondrial, membrane-associated, and secreted CAs form well-supported evolutionary lineages that primarily reflect diversification in regulation, cellular targeting and physiological roles, rather than changes in catalytic mechanism. Catalytically inactive CA-related proteins (CARPs) constitute a distinct evolutionary branch derived from gene duplication and functional divergence of catalytically active CAs. Molecular analyses reveal strong evolutionary constraints on residues essential for zinc coordination and proton transfer, whereas surface-exposed and regulatory regions show greater evolutionary flexibility. Comparative analyses across vertebrates highlight the broad conservation of major CA clades, together with lineage-specific differences in isoform repertoires. By embedding functional interpretation within a phylogenetic framework, this chapter provides an evolutionary basis for comparative and biomedical studies of vertebrate CAs.","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"59 ","pages":"1-27"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148563254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Remodeling at the intersection of time and tissue: Aging, obesity, and the MT1-MMP proteolytic driver in ovarian cancer. 在时间和组织的交叉点重塑：卵巢癌的衰老、肥胖和MT1-MMP蛋白水解驱动因素。

Enzymes Pub Date : 2026-01-01 Epub Date: 2026-09-14 DOI: 10.1016/bs.enz.2026.07.002

Brighton C Strasiotto, Mary Sharon Stack

{"title":"Remodeling at the intersection of time and tissue: Aging, obesity, and the MT1-MMP proteolytic driver in ovarian cancer.","authors":"Brighton C Strasiotto, Mary Sharon Stack","doi":"10.1016/bs.enz.2026.07.002","DOIUrl":"https://doi.org/10.1016/bs.enz.2026.07.002","url":null,"abstract":"Ovarian cancer is the leading cause of gynecological cancer death for women in the United States. Aging and obesity are known risk factors that increase incidence rate, severity, and metastatic progression of ovarian cancer. With aging and obesity, physiological changes occur including increased inflammation, altered metabolism, and, most notably, extracellular matrix (ECM) remodeling. Remodeling of the ECM is critical for accommodating adipocyte expansion in obesity and arises from accumulated modifications with aging. The already remodeled collagen under these host factors is driven by remodeling enzymes such as matrix metalloproteinases (MMPs). Of particular interest is membrane-bound MT1-MMP, which is required for invasion in metastatic ovarian cancer. MT1-MMP is responsible for the directed collagenolysis of the ECM, which is a barrier to metastatic growth. Because of metastatic dependence on MT1-MMP, there have been many attempts to inhibit this enzyme, but current therapies lack specificity and cause significant adverse side effects. Nonetheless, novel therapeutic interventions targeting MT1-MMP are promising to improve selectivity. In this chapter, we will highlight key pathways regulating MT1-MMP expression, impact on oncogenic phenotypes, and the mechanisms that aging and obesity use to further promote ECM remodeling and accelerate disease progression, while assessing past and future challenges to study and targeting MMPs for cancer treatment.","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"60 ","pages":"281-316"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149026390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Activity-based probes to detect MMP activity. 用于检测MMP活动的基于活动的探针。

Enzymes Pub Date : 2026-01-01 Epub Date: 2026-06-27 DOI: 10.1016/bs.enz.2026.06.003

Konstantinos Patiniotis, Dimitris Georgiadis, Laurent Devel

{"title":"Activity-based probes to detect MMP activity.","authors":"Konstantinos Patiniotis, Dimitris Georgiadis, Laurent Devel","doi":"10.1016/bs.enz.2026.06.003","DOIUrl":"https://doi.org/10.1016/bs.enz.2026.06.003","url":null,"abstract":"Elucidating the precise biological functions of MMPs remains challenging because conventional analytical methods generally measure total protein abundance rather than enzymatic activity. Since only a fraction of the enzyme pool exists in an active form and proteolytic activity is the primary determinant of MMP function, approaches capable of selectively monitoring active MMPs provide a more accurate representation of their physiological and pathological roles. Recent advances in chemical biology have led to the development of molecular probes that directly interrogate MMP activity in complex biological environments. This chapter reviews two complementary classes of probes: substrate-based activatable probes and affinity-based probes. Activatable probes exploit MMP-mediated cleavage to generate detectable signals and enable sensitive monitoring of proteolytic activity in cells, tissues, biological fluids, and living organisms. In contrast, affinity-based probes selectively bind active MMPs and form covalent adducts that enable their direct visualization, enrichment, and unambiguous identification by proteomic methods. Particular emphasis is placed on probe design, substrate selectivity, analytical performance, and applications ranging from in vivo imaging to activity-based biomarker discovery. Finally, current limitations and emerging opportunities are discussed, including machine learning-guided substrate design, synthetic biomarker technologies, and next-generation affinity-based profiling strategies, which collectively hold promise for advancing both fundamental MMP biology and translational diagnostic applications.","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"60 ","pages":"37-73"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149026337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Carbonic anhydrase XIV. 碳酸酐酶。

Enzymes Pub Date : 2026-01-01 Epub Date: 2026-06-22 DOI: 10.1016/bs.enz.2026.06.002

Giuseppina De Simone, Vincenzo Alterio

引用次数: 0

Classical MMP inhibitors. 经典的MMP抑制剂。

Enzymes Pub Date : 2026-01-01 Epub Date: 2026-08-06 DOI: 10.1016/bs.enz.2026.07.003

Andrea Trabocchi

{"title":"Classical MMP inhibitors.","authors":"Andrea Trabocchi","doi":"10.1016/bs.enz.2026.07.003","DOIUrl":"https://doi.org/10.1016/bs.enz.2026.07.003","url":null,"abstract":"Considering the pivotal roles of matrix metalloproteinases (MMPs) in tumor progression, MMP inhibitors (MMPIs) have emerged as promising therapeutic agents, resulting in the development of several generations of inhibitors and candidate cancer drugs. First-generation inhibitors were conceived as peptide-based inhibitors and hydroxamate-based peptidomimetics such as batimastat and marimastat, demonstrating at preclinical level the strong anticancer activity by targeting the catalytic Zn²⁺ ion of MMPs. Nevertheless, their clinical success was limited by poor bioavailability and selectivity, resulting to severe side-effects. Second-generation MMPIs consisted of alternative zinc-binding groups, such as thiol, carboxylic acid, pyrimidine, and hydroxypyrone moieties compounds, resulting in failure in clinical trials of improved candidate drugs such as prinomastat and tanomastat due to low oral bioavailability and safety concerns. A major issue has been the non-specific inhibition across multiple MMP family members due to high conservation of the MMP catalytic site. Herein is summarized the development of MMP inhibitors and are described those compounds that reached clinical trials. It is expected that advances in structural biology highlighting the structural differences among MMPs may facilitate the development of more selective inhibitors with improved efficacy and reduced toxicity and enable new MMPI as candidate cancer drugs.","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"60 ","pages":"75-99"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149026376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0