Article
Psychiatry
David C. Stoppel, Patrick K. McCamphill, Rebecca K. Senter, Arnold J. Heynen, Mark F. Bear
Summary: Fragile X syndrome is caused by silencing of the human FMR1 gene and is the leading monogenic cause of intellectual disability and autism. Studies indicate that long-term use of mGluR5 NAMs may lead to the development of treatment resistance, likely occurring at signaling nodes downstream.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Pier Francesca Porceddu, Mariasole Ciampoli, Elisa Romeo, Beatrice Garrone, Lucia Durando, Claudio Milanese, Francesco Paolo Di Giorgio, Angelo Reggiani
Summary: Glycogen-synthase kinase 3 (GSK3) is a kinase involved in the regulation of various cellular processes and its dysregulation has been linked to diseases such as fragile X syndrome (FXS). This study used a potent GSK3 inhibitor in an FXS mouse model and found that behavioral abnormalities were reversed, highlighting the significance of GSK3 as a therapeutic target.
HUMAN MOLECULAR GENETICS
(2022)
Review
Biochemistry & Molecular Biology
Divya M. Teli, Anuradha K. Gajjar
Summary: Elevated glucose level due to β-cell dysfunction is a key marker of Type-II diabetes. GSK-3, an enzyme involved in glycogen metabolism control, has been explored for its potential as a target for diabetes treatment. This review article examines the structural analysis and molecular modeling of GSK-3, as well as advancements in the development of GSK-3 inhibitors as potential therapeutics for Type II diabetes.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Mahdi Rizk, Zahraa Saker, Hayat Harati, Youssef Fares, Hisham F. Bahmad, Sanaa Nabha
Summary: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted interests, repetitive behaviors, and deficits in social communication. Syndromic ASD, caused by underlying genetic disorders such as Fragile X Syndrome (FXS) and Rett Syndrome (RTT), may involve dysfunction of the core signaling pathway GSK3, which plays a crucial role in the pathogenesis of ASD, FXS, and RTT.
MOLECULAR BIOLOGY REPORTS
(2021)
Article
Multidisciplinary Sciences
Samuel M. Law, Jie J. Zheng
Summary: Wnt signaling pathways play a significant role in various diseases. β-catenin is central to the canonical Wnt signaling pathway. CHIR-99021, a GSK-3β inhibitor, is widely used for studying this pathway. However, caution is needed when using CHIR-99021 at certain concentrations.
Article
Fisheries
Xiaotong Sun, Hongtao Nie, Xiwu Yan
Summary: This study identified and investigated three novel glycogen metabolism-related proteins in Manila clam, suggesting their potential involvement in innate immunity and important role in immune defense.
Review
Biochemistry & Molecular Biology
Chia-Ling Chen, Po-Chun Tseng, Rahmat Dani Satria, Thi Thuy Nguyen, Cheng-Chieh Tsai, Chiou-Feng Lin
Summary: GSK-3 is a vital regulator of glycogen synthesis that plays a crucial role in cellular bioregulation. Abnormal GSK-3 activation and inactivation can lead to liver damage. Targeting GSK-3 with drugs is a potential therapeutic approach for liver protection. Additionally, blocking GSK-3 has a protective effect in IFN-gamma-mediated immune hepatitis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Parisa Badiee, Michelle F. Maritz, Benjamin Thierry
Summary: A nanoformulation of a small molecule GSK3 inhibitor has been developed as a potential alternative to antibody-based checkpoint inhibition. The nanoformulation efficiently inhibits PD-1 expression and improves the survival and proliferation of CAR-T cells, while also increasing the population of memory T cells.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Multidisciplinary Sciences
Long He, Jennifer Endress, Sungyun Cho, Zhongchi Li, Yuxiang Zheng, John M. Asara, John Blenis
Summary: Serine/one-carbon metabolism plays a critical role in cancer cell growth, but the regulatory mechanisms are not well understood. This study reveals that glycogen synthase kinase 3 (GSK3) plays a key role in regulating the expression of serine/one-carbon metabolic enzymes. Inhibition of nuclear GSK3 signaling enhances the efficacy of serine/one-carbon metabolism inhibitors in suppressing cancer cell proliferation.
Article
Neurosciences
B. Di Marco, P. Dell'Albani, S. D'Antoni, M. Spatuzza, C. M. Bonaccorso, S. A. Musumeci, F. Drago, B. Bardoni, M. V. Catania
Summary: The study found a novel modulatory role of mGlu5 receptor in SGs formation, providing new perspectives for understanding cellular response to stress in FXS pathophysiology.
NEUROBIOLOGY OF DISEASE
(2021)
Review
Cell Biology
Ryan T. McCallum, Melissa L. Perreault
Summary: This study discussed the widespread multi-system involvement of GSK-3 in contributing to the neuropathology of MDD, emphasizing the feed-forward mechanistic links between all major neuronal signaling pathways.
Article
Biochemistry & Molecular Biology
Byung Geun Ha, Jung-Yoon Heo, Yu-Jin Jang, Tae-Shin Park, Ju-Yeon Choi, Woo Young Jang, Sung-Jin Jeong
Summary: The study revealed that mitochondrial dysfunction in astrocytes of FXS model mice is associated with the pathogenesis of the disease, and can be monitored by depletion of mitochondrial components in EVs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Analytical
Xuejiao Dong, Jianan Sun, Weili Miao, Chia-en A. Chang, Yinsheng Wang
Summary: The study utilized isotope-coded ATP acyl-phosphate probes and a targeted proteomic method to identify endogenous kinases that can bind to N-6-modified ATP derivatives. Among the quantified kinases, 27 and 18 were found to bind to KTP and N-6-Me-ATP respectively, with GSK3 alpha and GSK3 beta being able to bind to both ATP analogues. Biochemical assays demonstrated that GSK3 beta utilizes N-6-Me-ATP but not KTP as the phosphate group donor for phosphorylation.
ANALYTICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Katharina Jans, Kai Luersen, Jakob von Frieling, Thomas Roeder, Gerald Rimbach
Summary: A study found that dietary lithium can significantly improve fruit fly egg production by regulating the mRNA levels of genes related to follicular maturation. This is the first report of dietary lithium acting as a stimulant for fecundity in fruit flies.
Article
Biochemistry & Molecular Biology
Chantalle Moolman, Rencia van der Sluis, Richard M. Beteck, Lesetja J. Legoabe
Summary: Plasmodium falciparum glycogen synthase kinase-3 (PfGSK-3) has been identified as a potential target for the development of novel drugs against multi-drug resistant malaria. A series of benzofuran-based compounds were synthesized and evaluated as inhibitors of PfGSK-3 and human glycogen synthase kinase-3 beta (HsGSK-3 beta). Among these compounds, five preferentially inhibited PfGSK-3, with four exhibiting IC50 values in the sub-micromolar range. Evaluation of the structure-activity relationships revealed potential for future design of PfGSK-3 selective inhibitors using chalcone-based scaffolds like benzofurans.
BIOORGANIC CHEMISTRY
(2021)
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)