Article
Cell Biology
Jiayin Li, Peixuan Dang, Zhen Li, Tujing Zhao, Daojun Cheng, Dingyu Pan, Yufeng Yuan, Wei Song
Summary: This study reveals that Akh enhances carbohydrate production in the fat body and leads to hyperglycemia by phosphorylating ERK and translocating it to peroxisome via the CaMKII cascade. The findings demonstrate that the Akh/glucagon-peroxisomal-ERK axis is a key spatial regulator of glycemic control.
Article
Immunology
Junkai Huang, Xiaoyue Feng, Jie Zeng, Shuchang Zhang, Jing Zhang, Pan Guo, Haoyue Yu, Mengke Sun, Jiangmei Wu, Mengyan Li, Yingxi Li, Xiaohua Wang, Lizhi Hu
Summary: This study elucidated the role of Nrf2 in TPA-induced acute ICD, showing that Nrf2 knockout increased inflammatory response and neutrophil infiltration, while decreasing the expression of antioxidant genes. Moreover, the ERK signaling pathway played a key role in TPA-induced inflammation and ROS accumulation.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Endocrinology & Metabolism
Gurhan Guney, Mine Islimye Taskin, Nazli Sener, Ezgi Tolu, Yavuz Dodurga, Levent Elmas, Orkun Cetin, Cengiz Sarigul
Summary: The study found that ERK-1 and ERK-2 genes play a crucial role in the pathogenesis of PCOS, and are related to BMI, FGS, HOMA-IR, and CRP levels.
REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY
(2022)
Article
Oncology
Jialin Mo, Fang Liu, Xi Sun, Hongting Huang, Kezhe Tan, Xiaojing Zhao, Rui Li, Wenyan Jiang, Yi Sui, Xiaosong Chen, Kunwei Shen, Liye Zhang, Jie Ma, Kewen Zhao, Yujie Tang
Summary: The study identifies FACT inhibition as an effective strategy for overcoming resistance to Smoothened inhibitors and provides preclinical support for initiating clinical trials of the FACT-targeted drug CBL0137 against hedgehog-driven cancers.
Article
Biochemistry & Molecular Biology
Meiling Wang, Jie Liu, Yizeng Tu, Zihan Zhao, Jingjing Qu, Ka Chen, Yonglong Chen, Ying Sun, Hui Zhao, Yi Deng, Chuanyue Wu
Summary: Our study reveals that the focal adhesion protein RSU1 plays a critical role in suppressing ERK signaling during cell-ECM detachment through its interaction with prohibitin 2 (PHB2) in lipid rafts. The binding between RSU1 and PHB2 at specific sites is essential for the activation of ERK signaling in response to ECM adhesion. When cells detach from ECM, RSU1 associates with lipid rafts and interacts with PHB2, ultimately leading to downregulation of ERK signaling.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Ulrich Blache, Stefania L. Wunderli, Amro A. Hussien, Tino Stauber, Gabriel Flueckiger, Maja Bollhalder, Barbara Niederoest, Sandro F. Fucentese, Jess G. Snedeker
Summary: The study shows that the ERK pathway plays a central role in tendon degradation during mechanical unloading, and pharmacological inhibition of ERK 1/2 can prevent loss of mechanical properties and suppress features of pathological tissue remodeling in unloaded tendons.
SCIENTIFIC REPORTS
(2021)
Article
Biology
Sumiko Takao, Lauren Forbes, Masahiro Uni, Shuyuan Cheng, Jose Mario Bello Pineda, Yusuke Tarumoto, Paolo Cifani, Gerard Minuesa, Celine Chen, Michael G. Kharas, Robert K. Bradley, Christopher R. Vakoc, Richard P. Koche, Alex Kentsis
Summary: The dysregulated gene expression in human cancers is often attributed to aberrant assembly of transcriptional co-activator complexes, as demonstrated in the case of acute myeloid leukemia (AML) subtypes. Targeted interference with MYB:CBP/P300 complexes can induce myeloid differentiation and apoptosis, providing a unified mechanism for oncogenic gene expression in AML. This study establishes a promising strategy for pharmacologic reprogramming and therapeutic targeting in diverse leukemias and potentially other human cancers.
Article
Biochemistry & Molecular Biology
Kelley Ingram, Shiela C. Samson, Rediet Zewdu, Rebecca G. Zitnay, Eric L. Snyder, Michelle C. Mendoza
Summary: NKX2-1 suppresses ERK activity by inducing the ERK phosphatase DUSP6, inhibiting tumor growth and metastasis in lung adenocarcinoma.
Review
Cell Biology
Sanjay Mishra, Manish Charan, Ajeet Kumar Verma, Bhuvaneswari Ramaswamy, Dinesh Kumar Ahirwar, Ramesh K. Ganju
Summary: Ethnic differences in mTOR and ERK-1/2 signaling pathways may be associated with the development and progression of different human malignancies. While socioeconomic disparities contribute to the differences in cancer incidence rates among different ethnic groups, genetic and molecular variations also play a significant role in racial disparities in the development of malignancies. Further studies are needed to explore the significance of racial disparity in abnormal mTOR and ERK-1/2 kinase signaling pathways for potentially developing tailored anti-cancer therapies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Jason C. Porta, Bing Han, Alican Gulsevin, Jeong Min Chung, Yelena Peskova, Sarah Connolly, Hassane S. Mchaourab, Jens Meiler, Erkan Karakas, Anne K. Kenworthy, Melanie D. Ohi
Summary: This study reveals the structural characteristics of the human caveolin-1 complex using cryo-electron microscopy, providing new insights into its membrane remodeling activity and uncovering the roles of key regions of caveolin-1 in its function.
Article
Cell Biology
Anfei Liu, Yunting Li, Sitong Lu, Chunqing Cai, Fei Zou, Xiaojing Meng
Summary: Lung metastasis is a major cause of breast cancer-related death. Tumor microenvironment and secreted factors, such as STC1, play important roles in promoting the metastasis. STC1 enhances cancer cell invasiveness, promotes angiogenesis and lung fibroblast activation in the metastatic microenvironment. Mechanistically, STC1 mediates its effects through the upregulation of S100A4 via EGFR and ERK signaling. Knockdown of S100A4 diminishes STC1-induced lung metastasis. Additionally, JNK signaling pathway activates STC1 expression in breast cancer cells with lung-tropism.
CELL DEATH & DISEASE
(2023)
Article
Immunology
Eduardo I. Tognarelli, Angello Retamal-Diaz, Monica A. Farias, Luisa F. Duarte, Tomas F. Palomino, Francisco J. Ibanez, Claudia A. Riedel, Alexis M. Kalergis, Susan M. Bueno, Pablo A. Gonzalez
Summary: Herpes simplex viruses (HSV-1 and HSV-2) cause lifelong infections in humans and can result in mild or severe clinical manifestations. These viruses have evolved mechanisms to evade the host's immune system, including inhibiting the function of dendritic cells (DCs) and inducing their apoptosis. In this study, researchers found that inhibiting a signaling pathway called IRE-1 alpha improved the function of DCs infected with HSV-1 or HSV-2, suggesting that targeting this pathway may enhance immune responses to HSV infections.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Inorganic & Nuclear
Lingzhi Qiu, Qiaoyu Zhang, Donghui Wei, Rongqiang Tian, Zheng Duan
Summary: Density functional theory calculations were used to investigate the fragmentation mechanism of 1-phenylselenyl-phosphirane complex. The results reveal that the reaction proceeds via an asynchronous concerted pathway, with the lone pair of the adjacent phosphorus atom playing a crucial role in the process.
DALTON TRANSACTIONS
(2022)
Article
Multidisciplinary Sciences
Nora-Guadalupe P. Ramirez, Jeon Lee, Yue Zheng, Lianbo Li, Bryce Dennis, Didi Chen, Ashwini Challa, Vicente Planelles, Kenneth D. Westover, Neal M. Alto, Ivan D'Orso
Summary: This study revealed an undescribed modulator, ADAP1, that influences the fate of HIV-1 provirus. The experimental results showed that ADAP1 can enhance T cell signaling and facilitate the escape of latent HIV-1 by activating the ERK-AP-1 axis.
NATURE COMMUNICATIONS
(2022)
Article
Pathology
Divya Sahu, Jianya Huan, Huawei Wang, Debashis Sahoo, Darren E. Casteel, Richard L. Klemke, Gerry R. Boss, Donna E. Hansel
Summary: Bladder cancer invasion is linked to mTORC2 activity, with increased iNOS expression identified as a key factor in invasion.
AMERICAN JOURNAL OF PATHOLOGY
(2021)
Article
Cell Biology
Marco Zattoni, Chiara Garrovo, Elena Xerxa, Giada Spigolon, Gilberto Fisone, Krister Kristensson, Giuseppe Legname
Summary: This study demonstrates that changes in LTCCs and NMDARs activities can modulate PrPSc formation through ERK signaling, suggesting a potential link between synaptic plasticity pathways and prion conversion. Contrasting intracellular signals during synaptic plasticity may influence time-dependent prion conversion.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2021)
Article
Clinical Neurology
Maria Conte, Valentina Medici, Davide Malagoli, Antonio Chiariello, Alice Cirrincione, Annalisa Davin, Maia Chikhladze, Francesco Vasuri, Giuseppe Legname, Isidre Ferrer, Silvia Vanni, Gabriella Marcon, Tino Emanuele Poloni, Antonio Guaita, Claudio Franceschi, Stefano Salvioli
Summary: The study found that perilipins are expressed in the human brain, with only Plin2 being modulated with age and neurodegeneration and linked to an inflammatory state. The accumulation of lipid droplets decorated with Plin2 may be an early marker and initial step in inflammation and neurodegeneration during brain aging.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Arianna Luise, Elena De Cecco, Erika Ponzini, Martina Sollazzo, PierLuigi Mauri, Frank Sobott, Giuseppe Legname, Rita Grandori, Carlo Santambrogio
Summary: Post-translational modifications can lead to diverse functional roles for a single protein, with oxidation being a common modification. Analyzing the interaction of proteins with dopamine and characterizing the proteoforms generated by dopamine-induced oxidation through top-down fragmentation can provide insights into the structural changes and relative abundance of different protein states.
Review
Cell Biology
Elisa Uliassi, Lea Nikolic, Maria Laura Bolognesi, Giuseppe Legname
Summary: This article reviews the major advances in prion drug discovery, including the identification of anti-prion small molecules through screening methods, as well as the discovery of novel compounds with expanded anti-prion profiles through multi-target-directed ligand (MTDLs) strategies and theranostics.
CELL AND TISSUE RESEARCH
(2023)
Article
Neurosciences
Lara Masperone, Marta Codrich, Francesca Persichetti, Stefano Gustincich, Silvia Zucchelli, Giuseppe Legname
Summary: The cellular prion protein (PrP(C)) interacts with TRAF6 protein, resulting in the redistribution and aggregation of PrP(C) through indirect modulation of PrP(C) ubiquitination. This novel interaction may uncover possible mechanisms of cell clearance and reorganization in prion diseases.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Cell Biology
Chiara Maria Giulia De Luca, Alessandra Consonni, Federico Angelo Cazzaniga, Edoardo Bistaffa, Giuseppe Bufano, Giorgia Quitarrini, Luigi Celauro, Giuseppe Legname, Roberto Eleopra, Fulvio Baggi, Giorgio Giaccone, Fabio Moda
Summary: Olfactory mucosa samples from patients with Parkinson's disease and multiple system atrophy can induce inflammatory responses by seeding the aggregation of alpha-synuclein. Distinct morphological features of alpha-synuclein aggregates can influence the inflammatory response in cells. The composition of alpha-synuclein strains and other factors in the tissue can modulate the biochemical, morphological, and inflammatory features of alpha-synuclein aggregates.
Article
Neurosciences
Marco Zattoni, Marika Mearelli, Silvia Vanni, Arianna Colini Baldeschi, Thanh Hoa Tran, Chiara Ferracin, Marcella Catania, Fabio Moda, Giuseppe Di Fede, Giorgio Giaccone, Fabrizio Tagliavini, Gianluigi Zanusso, James W. Ironside, Isidre Ferrer, Giuseppe Legname
Summary: This study investigated the differential expression of serpin superfamily members in neurodegenerative diseases. The results showed dysregulation of SERPINB1, SERPINB6, SERPING1, SERPINH1, and SERPINI1 in sCJD individuals compared to controls, while only SERPINB1 was upregulated in AD patients. Additionally, SerpinA3n transcript and protein were upregulated in a mouse model of AD. These findings suggest that SERPINA3/SerpinA3n may be a potential therapeutic target for the treatment of prion and prion-like neurodegenerative diseases.
MOLECULAR NEUROBIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Lea Nikolic, Chiara Ferracin, Giuseppe Legname
Summary: The article provides an overview of cellular models used in prion disease research, emphasizing the need for more relevant in vivo models and discussing the benefits and limitations of various cell-based models.
EXPERT OPINION ON DRUG DISCOVERY
(2022)
Article
Biochemistry & Molecular Biology
Rosalia Bruno, Laura Pirisinu, Geraldina Riccardi, Claudia D'Agostino, Elena De Cecco, Giuseppe Legname, Franco Cardone, Pierluigi Gambetti, Romolo Nonno, Umberto Agrimi, Michele Angelo Di Bari
Summary: Gerstmann-Straussler-Scheinker disease (GSS) is a rare genetic prion disease. In this study, the transmissibility of GSS-F198S prions to voles and the induction of Tau deposits were investigated, revealing similarities between GSS-F198S and familial Alzheimer's disease.
Article
Biology
Andrea Raspadori, Valentina Vignali, Anna Murello, Gabriele Giachin, Bruno Samori, Motomasa Tanaka, Carlos Bustamante, Giampaolo Zuccheri, Giuseppe Legname
Summary: Prion diseases are neurodegenerative disorders characterized by the presence of oligomers and amyloid fibrils. In this study, atomic force microscopy was used to investigate the conformational changes and oligomerization processes of the prion protein. The results showed a complex scenario of structural heterogeneity at the monomeric and dimer levels, and suggested that the C-C dimer orientation may play a role in amyloid fibril formation.
Article
Chemistry, Medicinal
Matteo Staderini, Silvia Vanni, Arianna Colini Baldeschi, Gabriele Giachin, Marco Zattoni, Luigi Celauro, Chiara Ferracin, Edoardo Bistaffa, Fabio Moda, Daniel Perez, Ana Martinez, M. Antonia Martin, Olmo Martin-Camara, Angel Cores, Giulia Bianchini, Robert Kammerer, J. Carlos Menendez, Giuseppe Legname, Maria Laura Bolognesi
Summary: This study designed novel carbazole derivatives as pharmacological chaperones for prion diseases. These derivatives showed anti-prion activity and could detect prion protein aggregates through fluorescent staining. The compounds exhibited activity against RML-infected cell lines and have potential applications in the treatment of prion diseases.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Giuseppe Legname
Summary: In mammals, the prion protein (PrPC) is a common protein involved in various functions in the central nervous system. It also plays a central role in prion diseases, a group of fatal neurodegenerative disorders. The protein can convert into an infectious form called prion and its unique structure, including octarepeat sequences and copper binding sites, may modulate prion conversion and replication.
Article
Cell Biology
Chiara Santulli, Carlotta Bon, Elena De Cecco, Marta Codrich, Joanna Narkiewicz, Pietro Parisse, Fabio Perissinotto, Claudio Santoro, Francesca Persichetti, Giuseppe Legname, Stefano Espinoza, Stefano Gustincich
Summary: This study identifies the significant role of hemoglobin (Hb) in the pathogenesis of Parkinson's disease. Long-term overexpression of Hb leads to the loss of dopaminergic neurons and motor and cognitive impairments. Hb also triggers the formation of endogenous C-terminal truncated species of α-synuclein.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Luigi Celauro, Marco Zattoni, Giuseppe Legname
Summary: Cellular prion protein plays a significant role in neurodegenerative diseases and can be taken up by neighboring cells. The intercellular routing of prion proteins involves the release through vesicles and nanotubes.
RECEPTOR ENDOCYTOSIS AND SIGNALLING IN HEALTH AND DISEASE, PT B
(2023)
Article
Chemistry, Multidisciplinary
Luigi Russo, Giulia Salzano, Andrea Corvino, Edoardo Bistaffa, Fabio Moda, Luigi Celauro, Gianluca D'Abrosca, Carla Isernia, Danilo Milardi, Gabriele Giachin, Gaetano Malgieri, Giuseppe Legname, Roberto Fattorusso
Summary: This study investigates the mechanism of thermal unfolding of human prion protein and reveals that the transient electrostatic interactions between the N- and C-terminal domains play a key role in regulating the folding process. The study also provides a clear molecular description of the initial phases of prion misfolding using fluorescence fibrillization assays.