Article
Virology
Maxim Cherneha, Johannes Korth, Meike Kaulfuss, Mirko Trilling, Marek Widera, Hana Rohn, Sebastian Dolff, Nina Babel, Andre Hoerning, Andreas Kribben, Oliver Witzke
Summary: Reactivations of BK polyoma virus and human cytomegalovirus can cause complications in renal transplant recipients. The phosphorylation of P70S6k in peripheral lymphocytes is associated with BKPyV reactivations and, to a lesser extent, with HCMV infections in these recipients, independent of immunosuppressive drug levels.
Article
Biochemistry & Molecular Biology
Takahisa Hirokawa, Taeko Horie, Yurie Fukiyama, Masashi Mimura, Shinji Takai, Teruyo Kida, Hidehiro Oku
Summary: The study identified that the overactivation of Cdk5 is associated with the development of tauopathies. Roscovitine, a Cdk5 inhibitor, reduces the phosphorylation level of tau protein and mitigates the pathologic phosphorylation of tau by inhibiting the calpain signaling pathway, thereby alleviating the degeneration of RGCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Li Lin, Xiaodong Liu, Xuejun Cheng, Yujing Li, Marla Gearing, Allan Levey, Xiaoli Huang, Ying Li, Peng Jin, Xuekun Li
Summary: In this study, the altered expression and misregulation of miR-650 in Alzheimer's disease (AD) brains were observed. Bioinformatic analysis predicted that miR-650 targets three AD-associated genes, and experimental confirmation showed that miR-650 significantly reduces their expression levels in vitro. Overexpression of miR-650 was shown to alter CDK5 levels and ameliorate AD pathologies in transgenic mice. These findings suggest that miR-650 influences AD pathogenesis through regulation of CDK5.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Xiaoyue Ji, Junhong Chen, Chaoying You, Jing Sun, Xiulong Xu
Summary: Leflunomide controls obesity in part by activating AMPK and inducing lipophagy.
Article
Multidisciplinary Sciences
Yuhan Yan, Chao Chen, Zhiguo Li, Jing Zhang, Narin Park, Cheng-Kui Qu
Summary: A continuous supply of exogenous arginine is crucial for the maintenance and function of normal hematopoietic stem cells (HSCs), but the L-arginine transporter CAT3 is dispensable for normal hematopoiesis and leukemogenesis.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Lorela Ciraku, Zachary A. Bacigalupa, Jing Ju, Rebecca A. Moeller, Giang Le Minh, Rusia H. Lee, Michael D. Smith, Christina M. Ferrer, Sophie Trefely, Luke T. Izzo, Mary T. Doan, Wiktoria A. Gocal, Luca D'Agostino, Wenyin Shi, Joshua G. Jackson, Christos D. Katsetos, Kathryn E. Wellen, Nathaniel W. Snyder, Mauricio J. Reginato
Summary: This study identifies a novel mechanism in which OGT regulates acetate-dependent acetyl-CoA and lipid production by regulating phosphorylation of ACSS2 by CDK5. The OGT/CDK5/ACSS2 pathway may be a potential target for treating altered metabolic dependencies in brain tumors.
Article
Oncology
Chun-hua Wang, Lu-kai Wang, Chang-chieh Wu, Mao-liang Chen, Chan-yen Kuo, Rong-yaun Shyu, Fu-ming Tsai
Summary: This study aimed to investigate the effects of TIG1 and mTOR signaling pathways associated with VAC14 on melanoma. The results showed that TIG1 was downregulated in malignant melanoma while VAC14 was upregulated. TIG1 inhibited the activation of mTOR signaling pathway by inhibiting VAC14, which may contribute to the prevention of malignant melanoma through retinoic acid via VAC14.
ANTICANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Eric B. Wright, Shinji Fukuda, Mingzong Li, Yu Li, George A. O'Doherty, Deborah A. Lannigan
Summary: The study identified a natural product, SL0101, that binds specifically to RSK1/2 by inducing conformational rearrangement, but not to RSK3/4 due to a single amino acid difference. Kinetic analysis revealed that regions outside of the N-terminal kinase domain also contribute to stable inhibitor binding towards RSK2. Additionally, a modification on SL0101 was discovered to form a highly stable inhibitor complex with RSK2, suggesting potential for identifying RSK2-specific inhibitors.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Hui Ma, Jiayan Cui, Zehui Liu, Wenqing Fang, Sisi Lu, Shuying Cao, Yuanyuan Zhang, Ji-An Chen, Lixue Lu, Qiong Xie, Yonghui Wang, Ying Huang, Kongfei Li, Hongyan Tong, Jin Huang, Weiqiang Lu
Summary: This study demonstrates that induction of degradation of FLT3-ITD protein by DHODH blockade may offer a promising therapeutic strategy for AML patients harboring FLT3-ITD mutation.
Review
Pathology
Junpeng Xu, Qingge Jia, Yan Zhang, Yuan Yuan, Tianqi Xu, Kangjie Yu, Jia Chai, Kaijing Wang, Ligang Chen, Tian Xiao, Mingyang Li
Summary: RSK4 is a Ser/Thr protein kinase that regulates cell survival and proliferation in various types of cancer. Its role as a tumor suppressor gene or an oncogene is controversial, and specific inhibitors for RSK4 have not been found.
PATHOLOGY RESEARCH AND PRACTICE
(2021)
Review
Cardiac & Cardiovascular Systems
Muna Suleiman, Afnan Al Najjar, Zain Z. Zakaria, Rashid Ahmed, Huseyin C. Yalcin, Hesham M. Korashy, Shahab Uddin, Sadaf Riaz, Nabeel Abdulrahman, Fatima Mraiche
Summary: Targeted therapy, such as TKIs, has been approved for managing cancer, but TKI-induced cardiotoxicity limits their use. Investigating potential cardioprotective techniques to combine with TKIs has become necessary.
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
(2023)
Article
Psychiatry
Caline S. Karam, Brenna L. Williams, Irina Morozova, Qiaoping Yuan, Rony Panarsky, Yuchao Zhang, Colin A. Hodgkinson, David Goldman, Sergey Kalachikov, Jonathan A. Javitch
Summary: Drug abuse, particularly of stimulants, is a significant public health issue with various complications. This study utilized the fruit fly model to investigate the transcriptional changes induced by amphetamines (AMPHs), identifying genes involved in mRNA translation control that were upregulated in response to AMPH. The findings contribute to our understanding of the molecular basis of drug addiction.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Neurosciences
Yu Zhao, Chuanling Wang, Wenbo He, Zhiyou Cai
Summary: Minocycline mitigates Alzheimer's-like pathology by limiting the activation of the Cdk5/p25 signaling pathway and improves cognitive deficits.
CURRENT NEUROPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Fabian Arechavaleta-Velasco, Pablo Dominguez-Lopez, Ernesto Acosta-Jimenez, Laura Diaz-Cueto
Summary: RSK4 promoter methylation is increased in malignant ovarian tumors, but this does not regulate its expression in ovarian cancer. Reactivation of RSK4 only reduces cell proliferation in the endometrioid histological subtype.
MOLECULAR BIOLOGY REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Hansol Lee, Yun-Jin Hwang, Jung-Hyun Park, Du-Hyong Cho
Summary: This study investigates the effect of valproic acid (VPA) on vascular smooth muscle cell (VSMC) proliferation and its mechanism. The results show that VPA decreases cell proliferation through PP2A-mediated inhibition of p-p70S6K-Thr(389). This suggests that VPA could be used in the treatment and prevention of atherosclerosis and in-stent restenosis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biology
Tao Ye, Yangyang Duan, Hayley W. S. Tsang, He Xu, Yuewen Chen, Han Cao, Yu Chen, Amy K. Y. Fu, Nancy Y. Ip
Summary: Researchers demonstrate a simple and precise method to simultaneously generate iPSC lines with different gene dosages using paired Cas9 nickases. As proof-of-concept they apply this method to examining amyloid precursor protein gene dosage effects in an Alzheimer's disease patient-derived iPSC line. Their method could potentially advance what we know about disease mechanisms and assist with gene therapy development.
COMMUNICATIONS BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Shun-Fat Lau, Amy K. Y. Fu, Nancy Y. Ip
Summary: Genetic analyses have shown the significant role of microglial dysfunction in Alzheimer's disease pathogenesis, with cytokine-induced microglial responses being a potential target for therapeutic development. However, the transition of microglial states induced by cytokines is complex and not fully understood, along with the mechanisms of how different functional states within this transition regulate AD pathology remaining unclear. This review summarizes the impact of various cytokine signaling pathways on microglial functions in AD and discusses the potential beneficial outcomes of modulating these pathways for therapeutic purposes.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Cell Biology
Peng Chen, Hongyang Jing, Mingtao Xiong, Qian Zhang, Dong Lin, Dongyan Ren, Shunqi Wang, Dongmin Yin, Yongjun Chen, Tian Zhou, Baoming Li, Erkang Fei, Bing-Xing Pan
Summary: The high-level expression of NRG1 leads to reduced dendritic spine density and decreased frequency of miniature excitatory postsynaptic currents. This is accompanied by activation of LIMK1 and increased cofilin phosphorylation in postsynaptic densities.
CELL DEATH & DISEASE
(2021)
Review
Neurosciences
Xiaopu Zhou, Yolanda Y. T. Li, Amy K. Y. Fu, Nancy Y. Ip
Summary: Alzheimer's disease poses a critical threat to human health due to its high prevalence among the elderly population and lack of effective treatments. Polygenic score models are being used to study the disease and are associated with clinical outcomes, brain imaging findings, and biochemical biomarkers. Incorporating polygenic score models into research and clinical practice may present potential challenges.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Physiology
Xia Dong, Tiankun Hui, Jie Chen, Zheng Yu, Dongyan Ren, Suqi Zou, Shunqi Wang, Erkang Fei, Huifeng Jiao, Xinsheng Lai
Summary: Metformin treatment improves muscle function and diminishes neuromuscular deficits in mdx mice, suggesting its potential use as a therapeutic drug in DMD patients.
FRONTIERS IN PHYSIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Ruolin Fan, Kwok-On Lai
Summary: Kinesin superfamily proteins (KIFs) are essential molecular motors that transport cargoes to both axons and dendrites of neurons, influencing synaptic development and plasticity. This review summarizes major kinesin motors and their associated cargoes, discussing their roles in regulating postsynaptic function in neurons.
Article
Neurosciences
Peng Chen, Ziyang Liu, Qian Zhang, Dong Lin, Lu Song, Jianghong Liu, Hui-Feng Jiao, Xinsheng Lai, Suqi Zou, Shunqi Wang, Tian Zhou, Bao-Ming Li, Li Zhu, Bing-Xing Pan, Erkang Fei
Summary: Mutations in cell adhesion molecules (CAMs) can lead to abnormal synapse formation and maturation, possibly contributing to autism spectrum disorders (ASDs). This study discovered that the DSCAM gene, a high-risk gene for autism, plays a role in preventing premature spine maturation and excessive glutamatergic transmission. Deficiency of DSCAM led to accelerated dendritic spine maturation and autism-like behaviors in mice.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Erkang Fei, Peng Chen, Qian Zhang, Yanzi Zhong, Tian Zhou
Summary: This study reveals that S10 phosphorylation of Dysbindin-1A by Akt1 is essential for neuronal development. Overexpression of wild type or S10 phospho-mimic mutant of Dysbindin-1A can rescue the dendrite and spine deficits in Dysbindin-1A knockdown neurons.
Article
Biochemistry & Molecular Biology
Min Yan, Mingtao Xiong, Yongqiang Wu, Dong Lin, Peng Chen, Jiang Chen, Ziyang Liu, Hang Zhang, Dongyan Ren, Erkang Fei, Xinsheng Lai, Suqi Zou, Shunqi Wang
Summary: This study found that the full length of LRP4 in the piriform cortex is necessary for maintaining synaptic plasticity and the integrity of olfactory function.
CELL AND BIOSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Nuojin Li, Tian Zhou, Erkang Fei
Summary: Metformin, a commonly prescribed drug for type 2 diabetes, has been found to improve cognitive and mood functions in patients and show potential benefits in treating neurological disorders. However, the exact mechanism of metformin in the brain is still not fully understood, but recent studies suggest that it may regulate neurotransmission and the balance of excitation and inhibition in neural networks.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Ying Dong, Xiong Pi, Frauke Bartels-Burgahn, Deniz Saltukoglu, Zhuoyi Liang, Jianying Yang, Frederick W. Alt, Michael Reth, Hao Wu
Summary: This study reports the cryo-electron microscopy structures of mouse full-length IgM BCR, revealing the organizing principle of BCR and providing insights into B cell signaling and therapeutic design against BCR-mediated diseases.
Article
Multidisciplinary Sciences
Zhuoyi Liang, Lijuan Zhao, Adam Yongxin Ye, Sherry G. Lin, Yiwen Zhang, Chunguang Guo, Hai-Qiang Dai, Zhaoqing Ba, Frederick W. Alt
Summary: Immunoglobulin heavy chain variable region exons are assembled in progenitor -B cells, with VH, D, and JH gene segments located in separate clusters. CTCF-binding elements (CBEs) in the IGCR1 element and 3' Igh-CBEs play a role in segregating different domains and impeding RAG scanning. Downregulation of WAPL in progenitor -B cells neutralizes CBEs and promotes VH-to-DJH rearrangements. The gradual WAPL downregulation mechanism and the reinforcement of CBEs contribute to ordered V(D)J recombination.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Neurosciences
Xianghe Li, Dongyan Ren, Bin Luo, Ziyang Liu, Nuojing Li, Tian Zhou, Erkang Fei
Summary: Anxiety disorder is a common mental disorder, affecting nearly 30% of adults worldwide, yet its molecular mechanisms remain unclear. A study on mice exposed to chronic restraint stress showed that anxiety-like behavior was induced and synaptic transmission in the medial prefrontal cortex was reduced. The reduction of perineuronal nets (PNNs) expression in the medial prefrontal cortex and the decrease of aggrecan (ACAN) levels were found to be associated with anxiety-like behavior. Treatment with the clinically prescribed antidepressant/anxiolytic drug Fluoxetine not only improved behavior and synaptic transmission deficits but also prevented the reduction of PNNs and ACAN expressions induced by chronic restraint stress. This study highlights the importance of proper PNNs levels in brain function and suggests that their decline may contribute to the pathogenesis of anxiety disorders.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Dongyan Ren, Bin Luo, Peng Chen, Lulu Yu, Mingtao Xiong, Zhiqiang Fu, Tian Zhou, Wen-Bing Chen, Erkang Fei
Summary: DGCR2 gene is upregulated during neurodevelopment and enriched in postsynaptic densities. Deficiency of DGCR2 leads to decreased spine formation, glutamatergic transmission, and synaptic plasticity in the hippocampus, resulting in abnormal behaviors. This study provides insight into the pathophysiological mechanism of DGCR2 in 22q11DS and related mental disorders, highlighting DGCR2 as a novel cell adhesion molecule required for spine development and synaptic plasticity.
CELL AND BIOSCIENCE
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Kwok-On Lai
JOURNAL OF NEUROCHEMISTRY
(2022)