Article
Physiology
Junghyun Kim, Ramasubramanian Baalachandran, Yue Li, Chen-Ou Zhang, Yunbo Ke, Pratap Karki, Konstantin G. Birukov, Anna A. Birukova
Summary: Extracellular histones released into the circulation can exacerbate endothelial dysfunction and acute lung injury by inducing inflammation and increasing permeability. These findings have important clinical significance in understanding the role of histones in disease progression.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2022)
Review
Immunology
Mridu Acharya, Shaun W. Jackson
Summary: This article introduces the evolutionary mechanisms that control the abnormal activation of endosomal Toll-like receptors, emphasizing the crucial role of B cells in the pathogenesis of systemic lupus erythematosus and how modulation of B cell endolysosomal flux tunes NA-sensing TLR activation signals.
IMMUNOLOGICAL REVIEWS
(2022)
Article
Immunology
Sean E. DeWolf, Sashi G. Kasimsetty, Alana A. Hawkes, Lisa M. Stocks, Sunil M. Kurian, Dianne B. McKay
Summary: This study demonstrates for the first time that endogenous DAMPs released from injured RTECs directly activate PRR signaling in healthy RTECs. These findings provide new insights for the treatment of renal IRI.
Article
Biochemistry & Molecular Biology
Marine Arnaud, Jordane Demonchy, Eden Arrii, Marta Luperto, Julien Lion, Sofiane Fodil, Stephanie Pons, Nuala Mooney, Lara Zafrani
Summary: The impact of extracellular histones on the immunogenicity of endothelial cells is unknown. This study found that histone-treated endothelial cells can induce the differentiation of suppressive Treg subpopulations and increase their expansion through an IL-6 and ICAM-1 dependent pathway. Further research is needed to evaluate the immunosuppressive effect of histone-induced endothelial cell activation on peripheral Treg cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Karsten Grote, Marina Nicolai, Uwe Schubert, Bernhard Schieffer, Christian Troidl, Klaus T. Preissner, Stefan Bauer, Silvia Fischer
Summary: The study demonstrated that self-extracellular RNA can interact with TLR2 ligands and enhance innate immune responses under pathological conditions, suggesting it as a new target for the treatment of bacterial and viral infections.
Article
Genetics & Heredity
Canan Eroglu Gunes, Fatma Secer Celik, Mucahit Secme, Levent Elmas, Yavuz Dodurga, Ercan Kurar
Summary: In this study, it was observed that oleandrin has an effect on genes and miRNAs associated with TLR pathway in melanoma cells. The pathways of TLRs and hsa-miR-146a-5p and hsa-miR-21-5p may participate in the molecular mechanism of action of oleandrin.
Article
Biochemistry & Molecular Biology
Lei Zhang, Guangshuai Liu, Tian Xia, Xiufeng Yang, Guolei Sun, Chao Zhao, Chunzhu Xu, Honghai Zhang
Summary: The study analyzed TLR genes from the genomes and transcriptomes of 102 amphibian species to understand their evolutionary patterns. Results showed that TLR genes can be divided into seven subfamilies, with TLR4 subfamily found only in Anura. Purification selection played a leading role in amphibian TLR evolution, and different domains had different evolution rates. Positive selection patterns and single-nucleotide polymorphisms were observed in TLR genes.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Medicine, Research & Experimental
Bin Zhang, Donghai Wu, Limei Hu, Xiaofeng Cha, Yilai Liu, Jujie Li, Bo Xie, Bin Li, Lei Zheng
Summary: Ligustilide selectively inhibits the proliferation of osteoblastoma cells by inducing apoptosis, possibly through TLR4-mediated endogenous and exogenous apoptotic mechanisms.
Article
Oncology
Xiaolei Cheng, Dongdong Jian, Junyue Xing, Cihang Liu, Yong Liu, Cunying Cui, Zhen Li, Shixing Wang, Ran Li, Xiaohan Ma, Yingying Wang, Xiaoping Gu, Zhenwei Ge, Hao Tang, Lin Liu
Summary: This study discovered a group of circulating miRNAs associated with dilated cardiomyopathy (DCM) and identified their important role in regulating myocardial apoptosis and autophagy. These miRNAs could serve as non-invasive diagnostic biomarkers for DCM and provide new insights into the pathogenesis and therapeutic targets of DCM.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Immunology
Sultan Alanazi, Fabio Rabelo Melo, Gunnar Pejler
Summary: This study reveals the significant role of tryptase in core histone processing and epigenetic modification in human mast cell leukemia cells, where inhibition of tryptase can reverse the effects of cell death on these modifications. The presence of tryptase in the nucleus suggests its involvement in regulating nuclear events and controlling cell proliferation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Irene Veneziani, Claudia Alicata, Lorenzo Moretta, Enrico Maggi
Summary: Toll-like receptors (TLRs) are described as homo- or heterodimeric proteins mainly in antigen presenting cells like dendritic cells (DCs), but recent studies have discovered their expression and role also in natural killer (NK) cells. The activation and function of TLRs can be modulated directly or indirectly by TLR agonists. The interplay between DCs and NK cells, mediated by cell-to-cell contact and soluble factors, promotes DC maturation and NK cell activation. Based on this concept, TLR-based immunotherapy targeting the NK-DC axis has been proposed to modulate the tumor microenvironment, improve DC antigen presentation, and enhance NK cell cytotoxicity against tumor cells.
IMMUNOLOGY LETTERS
(2023)
Review
Chemistry, Multidisciplinary
Xin Zhi, Peipei Yang, Yunxue Xu, Zhifei Dai, Xiuli Yue, Linxue Qian
Summary: This review discusses the functions of Toll-like receptors (TLRs) in the tumor microenvironment and the pathways that activate immune responses. It also summarizes recent developments in nanotechnology for immunomodulation with TLR agonists. Nanotechnology can improve the efficacy of TLR agonist-based immunotherapy and address its limitations.
Review
Biochemistry & Molecular Biology
Yuan-Tung Chu, Min-Tser Liao, Kuo-Wang Tsai, Kuo-Cheng Lu, Wan-Chung Hu
Summary: A comprehensive framework has been established to understand immunological pathways, and specific associations between immune responses and immune receptors have been identified. These findings contribute to the identification of biomarkers for immune cells and provide insights into host immunological pathways.
Review
Chemistry, Multidisciplinary
Mei Jin, Jian Fang, Jiao-jiao Wang, Xin Shao, Suo-wen Xu, Pei-qing Liu, Wen-cai Ye, Zhi-ping Liu
Summary: Atherosclerosis, a life-threatening cardiovascular disease, is associated with chronic inflammation and immune processes. Toll-like receptors (TLRs) play a vital role in the occurrence and development of atherosclerosis. Targeting TLRs and their regulated inflammatory events could be a promising new strategy for the treatment of atherosclerotic CVDs.
ACTA PHARMACOLOGICA SINICA
(2023)
Review
Biochemistry & Molecular Biology
Xiaoyan Lin, Siyu Ouyang, Chenxi Zhi, Pin Li, Xiaoqian Tan, Wentao Ma, Jiang Yu, Tianhong Peng, Xi Chen, Liang Li, Wei Xie
Summary: Vascular endothelial cells (VECs) are in direct contact with metabolite-related endogenous danger signals in the circulatory system. VECs death impairs vasodilation and increases endothelium-dependent permeability, which is strongly correlated with the development of atherosclerosis. Regulatory death of endothelial cells frequently occurs in atherosclerosis, including ferroptosis, pyroptosis, apoptosis and autophagy. This review summarizes regulatory factors and signaling mechanisms of regulatory death in endothelial cells, discussing their effects in the context of the atherosclerotic procession.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Cardiac & Cardiovascular Systems
Daniel Perez-Cremades, Jingshu Chen, Carmel Assa, Mark W. Feinberg
Summary: Diabetes mellitus is a global public health problem that is expected to continue increasing due to the rise in obesity and aging population. Individuals with diabetes have a higher risk of cardiovascular complications, particularly myocardial infarction (MI). In the past two decades, studies have revealed the role of stage-specific miRNAs in the hearts of people with diabetes and MI, impacting cardiomyocyte death, angiogenesis, inflammatory response, myocardial remodeling, and myocardial lipotoxicity. Understanding the significance of these miRNAs and their targets may lead to novel RNA-based therapeutic interventions for managing the increased risk of MI in diabetes.
TRENDS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Peripheral Vascular Disease
Michael G. McCoy, Anurag Jamaiyar, Grasiele Sausen, Henry S. Cheng, Daniel Perez-Cremades, Rulin Zhuang, Jingshu Chen, Philip P. Goodney, Mark A. Creager, Marc S. Sabatine, Marc P. Bonaca, Mark W. Feinberg
Summary: Peripheral artery disease (PAD) is a serious condition that can lead to limb loss and death, especially in subjects with diabetes. In this study, researchers identified miR-375 as a potential therapeutic target for critical limb ischemia (CLI), an advanced form of PAD. They found that miR-375, when overexpressed, promotes angiogenesis and arteriogenesis, improving blood flow recovery in diabetic mice. Further investigation revealed that miR-375 regulates the NF-kB signaling pathway by targeting Kruppel-like factor 5 (KLF5). These findings suggest that targeting the miR-375-KLF5-NF-kB signaling axis may be an effective strategy for treating CLI in diabetes.
Review
Biochemistry & Molecular Biology
Ahlam Fatmi, Wiam Saadi, Jesus Beltran-Garcia, Jose Luis Garcia-Gimenez, Federico Pallardo
Summary: Sepsis in newborns, especially preterm-born neonates, carries a significant risk of morbidity and mortality. Endothelial glycocalyx (eGC) shedding is an essential pathophysiological process in sepsis, contributing to microvascular dysfunction and organ failure. These processes have been extensively studied in adults, but are poorly understood in neonatal sepsis. Further research is needed to understand the composition, development, and mechanisms of eGC disruption in neonates, and to explore eGC dysfunction as a diagnostic and prognostic biomarker.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Carlos Roma-Mateo, Sheila Lorente-Pozo, Lucia Marquez-Thibaut, Mireia Moreno-Estelles, Concepcion Garces, Dayme Gonzalez, Marcos Lahuerta, Carmen Aguado, Jose Luis Garcia-Gimenez, Pascual Sanz, Federico V. V. Pallardo
Summary: Lafora disease is a rare, fatal form of progressive myoclonus epilepsy characterized by intracellular accumulation of abnormal polyglucosan granules. Experimental mouse models deficient in laforin or malin proteins provide evidence of molecular and cellular alterations in neural tissue. Overexpression of miR-155 and miR-146a in an age-dependent manner and altered gene expression in brain extracts indicate their potential role as biomarkers for disease progression in LD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Daniel Perez-Cremades, Carlos Bueno-Beti, Jose Luis Garcia-Gimenez, Jose Santiago Ibanez-Cabellos, Federico Pallardo, Carlos Hermenegildo, Susana Novella
Summary: This study reveals that extracellular histones can increase endothelial cell activation by increasing cytosolic reactive oxygen species production and triggering the overexpression of cell adhesion molecules. The study also identifies cyclooxygenase and NADPH oxidase as sources of reactive oxygen species production. These findings enhance our understanding of how extracellular histones contribute to systemic inflammatory responses in diseases.
JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
(2023)
Review
Oncology
Wiam Saadi, Ahlam Fatmi, Federico Pallardo, Jose Luis Garcia-Gimenez, Salvador Mena-Molla
Summary: Many non-coding RNAs play a role in cancer by controlling immune regulatory proteins, enabling tumor cells to evade the immune response. Understanding the mechanisms of these RNAs is crucial for developing therapeutic strategies and improving cancer immunotherapy. The focus of this review is to describe the role of long non-coding RNAs (lncRNAs) and their targets in regulating immune checkpoints.
Article
Medicine, Research & Experimental
Jose Luis Garcia-Gimenez, Eva Garcia-Lopez, Salvador Mena-Molla, Jesus Beltran-Garcia, Rebeca Osca-Verdegal, Elena Nacher-Sendra, Carmen Aguado-Velasco, German Casabo-Valles, Carlos Roma-Mateo, Maria Rodriguez-Gimillo, Oreto Antunez, Jose Ferreres, Federico V. Pallardo, Nieves Carbonell
Summary: This study validates a quantitative mass spectrometry method to measure circulating histone levels in plasma samples for the diagnosis and prognosis of sepsis and septic shock patients. In an extended laboratory testing, it was found that circulating histone levels are associated with the severity of patient conditions and can predict fatal outcomes.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Medicine, Research & Experimental
Henry S. Cheng, Rulin Zhuang, Daniel Perez-Cremades, Jingshu Chen, Anurag Jamaiyar, Winona Wu, Grasiele Sausen, Aspasia Tzani, Jorge Plutzky, Jorge Henao-Mejia, Philip P. Goodney, Mark A. Creager, Marc S. Sabatine, Marc P. Bonaca, Mark W. Feinberg
Summary: Patients with peripheral artery disease (PAD) and diabetes have a high risk of critical limb ischemia (CLI) and amputation. Dysregulated miRNAs from diabetic individuals with PAD and diabetic mice with limb ischemia revealed conserved miR-181 family members. High-fat-fed, diabetic Mir181a2b2-KO mice had impaired revascularization due to abrogation of circulating Ly6Chi monocytes. M2-like KO macrophages under diabetic conditions failed to produce proangiogenic cytokines.
Article
Cardiac & Cardiovascular Systems
Carlos Bueno-Beti, Clarice X. Lim, Alexandros Protonotarios, Petra Lujza Szabo, Joseph Westaby, Mario Mazic, Mary N. Sheppard, Elijah Behr, Ouafa Hamza, Attila Kiss, Bruno K. Podesser, Markus Hengstschlaeger, Thomas Weichhart, Angeliki Asimaki
Summary: This study characterizes the cardiac phenotype of mice with chronic activation of mTOR complex 1 signaling in myeloid cells, leading to spontaneous granulomatous inflammation similar to sarcoidosis. Treatment with the mTOR inhibitor everolimus resolved granulomatous infiltrates, prevented fibrosis, and improved cardiac dysfunction. This research presents a potential therapeutic option for patients with cardiac sarcoidosis.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Review
Clinical Neurology
Martha Cecilia Pineros-Fernandez, Beatriz Morte, Jose Luis Garcia-Gimenez
Summary: Whole exome sequencing (WES) plays an important role in the diagnosis of pediatric-onset neuromuscular diseases (NMD), helping to determine genetic diagnosis and treatment selection, especially in cases where other technologies have failed or in complex situations.
NEUROLOGICAL SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
M. T. Ciubuc-Batcu, N. J. C. Stapelberg, J. P. Headrick, G. M. C. Renshaw
Summary: The nervous system relies on mitochondria, and impaired mitochondrial function is associated with major depressive disorder. Modulating mitochondrial function may be a therapeutic target for treating MDD.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Correction
Biochemistry & Molecular Biology
Saowaluk Saisomboon, Ryusho Kariya, Piyanard Boonnate, Kanlayanee Sawanyawisuth, Ubon Cha'on, Vor Luvira, Yaovalux Chamgramol, Chawalit Pairojkul, Wunchana Seubwai, Atit Silsirivanit, Sopit Wongkham, Seiji Okada, Sarawut Jitrapakdee, Kulthida Vaeteewoottacharn
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Pavan Thapak, Zhe Ying, Victoria Palafox-Sanchez, Guanglin Zhang, Xia Yang, Fernando Gomez-Pinilla
Summary: Traumatic brain injury (TBI) impairs cellular energy demand, compromising neuronal function and plasticity. This study demonstrates that the mitochondrial activator humanin (HN) can counteract the reduction in mitochondrial bioenergetics caused by TBI, restore memory function and synaptic protein levels, and suppress inflammation and astrocyte proliferation. HN plays an integral role in normalizing fundamental aspects of TBI pathology.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
M. Paul Murphy, Valeria A. Buzinova, Carrie E. Johnson
Summary: Progress has been made in the treatment of Alzheimer's disease through the development of anti-A beta therapeutics, which have shown modest efficacy in slowing the progression of the disease. However, the puzzling issue remains as to why completely removing A beta does not fully stop the disease.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Review
Biochemistry & Molecular Biology
Yang Zhang, Mengqiu Hao, Xuyang Yang, Su Zhang, Junhong Han, Ziqiang Wang, Hai-Ning Chen
Summary: Colorectal cancer often requires adjuvant therapies to reduce tumor burden, and the efficacy of these therapies is significantly influenced by reactive oxygen species (ROS). ROS-mediated colorectal cancer adjuvant therapies involve multiple mechanisms, and preliminary clinical trials have shown the potential of ROS-manipulating therapy in enhancing treatment outcomes.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Mengxin Li, Xuanzhong Wang, Xuyang Chen, Jinghui Hong, Ye Du, Dong Song
Summary: Pancreatic adenocarcinoma (PAAD) is a common digestive malignant tumor with limited treatment options. This study demonstrates that TGM2 may serve as a marker for treatment and prognosis in pancreatic cancer patients. Co-treatment of low dose cisplatin (DDP) and the TGM2 inhibitor GK921 effectively inhibits PAAD cell viability and proliferation in vitro and in vivo, by inhibiting epithelial-to-mesenchymal transition (EMT) induced by TGM2 and enhancing cell cycle arrest and apoptosis caused by DDP. These findings suggest that the combination of GK921 and DDP holds promise as a treatment for PAAD patients.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Liaoran Niu, Qi Wang, Fan Feng, Wanli Yang, Zhenyu Xie, Gaozan Zheng, Wei Zhou, Lili Duan, Kunli Du, Yiding Li, Ye Tian, Junfeng Chen, Qibin Xie, Aqiang Fan, Hanjun Dan, Jinqiang Liu, Daiming Fan, Liu Hong, Jian Zhang, Jianyong Zheng
Summary: This review provides a comprehensive summary of the interaction between cancer cells and macrophages in the tumor microenvironment, and discusses the role of small extracellular vesicles (sEVs) in this process. It also explores the various effects of macrophage-secreted sEVs on tumor malignant transformation, and addresses the therapeutic advancements and challenges associated with these vesicles.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Neha Sawant, Sudhir Kshirsagar, P. Hemachandra Reddy, Arubala P. Reddy
Summary: Depression is a common neuropsychiatric comorbidity in Alzheimer's disease (AD) and other Tauopathies. Selective serotonin reuptake inhibitor (SSRI) treatment, such as Citalopram, not only has anti-depressive and anxiolytic effects, but also helps improve neurogenesis, reduce amyloid burden & Tau pathologies, and neuroinflammation in AD. In this study, Citalopram was found to reduce pathologically pTau level, increase synaptic gene expression and cytoskeletal structure, as well as improve cell survival, mitochondrial respiration, and mitochondrial morphology in cells expressing mutant APP and Tau. These findings suggest that Citalopram could be a promising therapeutic drug for treating depression and AD.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Yueqi Chen, Jiulin Tan, Chuan Yang, Zhiguo Ling, Jianzhong Xu, Dong Sun, Fei Luo
Summary: Bone is a self-healing organ that undergoes continuous regeneration through the cooperation of osteoclasts and osteoblasts. This study used ATAC-seq and RNA-Seq techniques to investigate the chromatin accessibility and transcriptomic landscape of osteoblast differentiation and mineralization. The results showed that global chromatin accessibility was extensively improved during osteoblastogenesis. Additionally, several transcription factors including MEF2A, PRRX1, Shox2, and HOXB13 were found to modulate the promoter accessibility of target genes during osteoblast differentiation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Zi-Ran Kang, Shanshan Jiang, Ji-Xuan Han, Yaqi Gao, Yile Xie, Jinxian Chen, Qiang Liu, Jun Yu, Xin Zhao, Jie Hong, Haoyan Chen, Ying-Xuan Chen, Huimin Chen, Jing-Yuan Fang
Summary: The study demonstrates that BCAA metabolism is involved in the development of colorectal cancer (CRC). BCAT2 deficiency promotes CRC progression by inhibiting BCAA metabolism and chronically activating the mTORC1 pathway.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Chao Zheng, Lingling Liu, Caiyun Liu, Fengna Chu, Yue Lang, Shan Liu, Yan Mi, Jie Zhu, Tao Jin
Summary: Inducing tolerogenic dendritic cells (tDCs) with low RelB expression could effectively alleviate symptoms and reduce immune cell infiltration and demyelination in experimental autoimmune encephalomyelitis (EAE) mouse model.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Hang Lam Li, Simei Go, Jung-Chin Chang, Arthur Verhoeven, Ronald Oude Elferink
Summary: This review highlights the distinct characteristics and crucial role of soluble adenylyl cyclase (sAC) in cellular processes, as well as recent significant advancements in the field of sAC research.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
M. Seco-Cervera, D. Ortiz-Masia, D. C. Macias-Ceja, S. Coll, L. Gisbert-Ferrandiz, J. Cosin-Roger, C. Bauset, M. Ortega, B. Heras-Moran, F. Navarro-Vicente, M. Millan, J. V. Esplugues, S. Calatayud, M. D. Barrachina
Summary: The study revealed the presence of resistance to apoptosis in complicated ileal Crohn's disease, with PDGFB inducing an ETS1-mediated resistance to apoptosis associated with an inflammatory and fibrogenic pattern of expression in intestinal fibroblasts. Potential targets against ileal fibrosis include PDGFRB, IL1R1, or MCL1.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Review
Biochemistry & Molecular Biology
Yunmeng Wang, Ping Cheng
Summary: Oncolytic viruses (OVs) are emerging as therapeutically relevant anticancer agents, especially when combined with genetically modified bispecific T cell engagers (BiTEs). This combination strategy can overcome the limitations of BiTEs alone and provide targeted cytotoxicity to solid tumors.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Stephanie Tannous, Hassan Y. Naim
Summary: Congenital sucrase-isomaltase deficiency (CSID) is an autosomal recessive disorder caused by variants in the SI gene. A frameshift mutation called c.273_274delAG (p.Gly92Leufs*8) has been identified in CSID patients in Greenlandic population, which leads to loss of digestive function of SI. Surprisingly, the truncated mutant can still be located on the cell surface and interacts with wild type SI, negatively affecting its enzymatic function. Furthermore, heterozygote carriers of this mutation may also exhibit CSID symptoms.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)