Review
Biochemistry & Molecular Biology
Mohammed Abul Kashem, Omar Sery, David Pow, Benjamin D. Rowlands, Caroline D. Rae, Vladimir J. Balcar
Summary: The studies reviewed provide insights into genetic factors influencing alcohol dependence, the intoxicating effects of alcohol, damage to brain cells caused by chronic excessive drinking, and potential molecular targets for addressing alcoholism and alcohol addiction. These findings could aid in predicting alcohol dependence risk, understanding the actions of alcohol, assessing brain damage, and guiding treatment and diagnosis strategies.
CURRENT MOLECULAR PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Dong Sun, Zhi-Bing Tan, Xiang-Dong Sun, Zhi-Peng Liu, Wen -Bing Chen, Leena Milibari, Xiao Ren, Ling-Ling Yao, Daehoon Lee, Chen Shen, Jin-Xiu Pan, Zhi-Hui Huang, Lin Mei, Wen-Cheng Xiong
Summary: The loss of NEO1 is associated with the development of epilepsy, as evidenced by reduced NEO1 expression in the hippocampi of epilepsy patients and elevated seizure susceptibility in Neo1 knockout mice. The interaction between NEO1 and GLAST in astrocytes plays a crucial role in regulating the epileptic phenotype by affecting GABAergic transmission and extracellular glutamate clearance. The findings suggest that NEO1 could be a potential therapeutic target for protecting the brain from epilepsy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Marc Dahlmanns, Jana Katharina Dahlmanns, Nicolai Savaskan, Hans-Herbert Steiner, Eduard Yakubov
Summary: Glial cells are essential for the proper function of the nervous system and play a role in maintaining the balance of extracellular glutamate levels. Dysregulation of glial glutamate transporters is seen in various neurological diseases. Rebalancing glial transporters could potentially be beneficial in the treatment of these diseases.
FRONTIERS IN BIOSCIENCE-LANDMARK
(2023)
Review
Biochemistry & Molecular Biology
Marc Dahlmanns, Jana Katharina Dahlmanns, Nicolai Savaskan, Hans-Herbert Steiner, Eduard Yakubov
Summary: Glial cells, such as astrocytes, oligodendrocytes, and microglial cells, play important roles in the function of the nervous system, including providing nutritive support, regulating synaptic transmission, and participating in the immune response. Glial cells are equipped with various glutamate transporters to maintain balanced extracellular glutamate levels and prevent excitotoxicity. Dysregulation of these transporters is observed in various CNS diseases, including glioma, epilepsy, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, leading to harmful effects on neuronal function. Targeting these transporters, such as system xc- and EAAT1/2, may have therapeutic benefits in treating these diseases.
FRONTIERS IN BIOSCIENCE-LANDMARK
(2023)
Article
Medicine, Research & Experimental
Qianyi Wu, Azman Akhter, Shashank Pant, Eunjoo Cho, Jin Xin Zhu, Alastair Garner, Tomoko Ohyama, Emad Tajkhorshid, Donald J. van Meyel, Renae M. Ryan
Summary: Glutamate is a crucial neurotransmitter in the mammalian CNS and its transport and regulation play a crucial role in maintaining proper CNS function. This study investigates the effects of specific mutations of the EAAT1 gene on CNS function and highlights the importance of ion channel and Cl- homeostasis in glia cells for the pathology of episodic ataxia type 6 (EA6). The study also identifies a novel mechanism involving ectopic Na+ leak conductance in glial cells.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biochemistry & Molecular Biology
Marina Gorostiola Gonzalez, Hubert J. Sijben, Laura Dall' Acqua, Rongfang Liu, Adriaan P. Ijzerman, Laura H. Heitman, Gerard J. P. van Westen
Summary: This study identified 105 unique somatic EAAT1 mutations in cancer patients and assessed their functional effects using in vitro assays. The results showed that these mutants have differential effects on the transport of glutamate and aspartate, as well as the inhibitory potency of certain inhibitors. The study also provided insights into the mechanism behind the observed functional effects using molecular dynamics simulations.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Zhi Nie, Dating Cheng, Chenglong Pan, Zhimin Wei, Chenyang Wang, Chunyan Wang
Summary: The study revealed that SH3BGRL3 is highly expressed in GBM and glioma stem cells, and its high expression is associated with poor survival in GBM patients. SH3BGRL3 is directly regulated by STAT3, forming a positive feedback loop that enhances the tumorigenic potential of GBM.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Review
Cell Biology
Falko Lange, Julia Hoernschemeyer, Timo Kirschstein
Summary: The progression of glioblastomas and tumor-associated epilepsy is closely linked through various pathophysiological mechanisms involving the neurotransmitter glutamate. Current research focuses on the role of glutamate receptors in these diseases and discusses future interventions to interfere with the glutamatergic network.
Review
Chemistry, Medicinal
Ronald Nicholas Laribee, Andrew B. Boucher, Saivikram Madireddy, Lawrence M. Pfeffer
Summary: This article explores the association between over-activation of autophagy and cell death in glioblastoma, as well as the inherent resistance of cancer stem cells to therapy. It suggests that autophagy promotes and maintains the stem-like state of cancer stem cells and contributes to their resistance to treatment.
Article
Cell Biology
Kefeng Ma, Anran Zhang, Xiaojun She, Honglian Yang, Kun Wang, Yingwen Zhu, Xiujie Gao, Bo Cui
Summary: High-intensity noise can cause permanent hearing loss, while short-duration medium-intensity noise only induces a temporary threshold shift and damages synapses formed by inner hair cells and spiral ganglion nerves. The study found that GLAST and Na+/K+-ATPase alpha 1 were co-localized in the cochlea and disrupted after noise exposure, potentially exacerbating the occurrence of synaptopathy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Neurosciences
Eduard Yakubov, Thomas Eibl, Alexander Hammer, Markus Holtmannspotter, Nicolai Savaskan, Hans-Herbert Steiner
Summary: Little progress has been made in the long-term management of malignant brain tumors, especially in the case of glioblastoma. Selenium may have positive effects in glioblastoma treatment, offering promising chances to overcome the current limitations in surgical treatment and radiochemotherapy outcomes.
FRONTIERS IN NEUROSCIENCE
(2021)
Review
Cell Biology
Weijia Fu, Xue Hou, Lihua Dong, Wei Hou
Summary: Glioblastoma (GBM) is a highly malignant brain tumor. The IL6/JAK/STAT3 signaling pathway plays a crucial role in the development and progression of GBM. Abnormal activation of STAT3 in GBM leads to immunosuppression and blocking this pathway can effectively inhibit tumor growth and metastasis. Inhibiting STAT3 may provide a new therapeutic approach for GBM, and combining STAT3 targeted therapy with conventional treatments could improve the current status of GBM treatment.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Oncology
Robyn A. Umans, Joelle Martin, Megan E. Harrigan, Dipan C. Patel, Lata Chaunsali, Aarash Roshandel, Kavya Iyer, Michael D. Powell, Ken Oestreich, Harald Sontheimer
Summary: Glioblastoma multiforme (GBM) is a deadly brain tumor with limited treatment options. Recent research suggests that tumor protein 53 (TP53) is a molecular regulator of System xc- (SXC) in GBM, with its expression negatively correlated with xCT expression. This finding indicates that p53 may serve as a potential therapeutic target for GBM by regulating glutamate biology.
Article
Neurosciences
Zuo-Xin Zhang, Peng Ren, Yong-Yong Cao, Ting-Ting Wang, Guo-Hao Huang, Yao Li, Shuo Zhou, Wei Yang, Lin Yang, Guo-Long Liu, Yan Xiang, Yu-Chun Pei, Qiu-Zi Chen, Ju-Xiang Chen, Sheng-Qing Lv
Summary: We aimed to investigate the mechanism of HOXD-AS2 in regulating temozolomide sensitivity in glioblastoma. Our results showed that elevated HOXD-AS2 expression promoted glioma progression and negatively correlated with prognosis. HOXD-AS2 attenuated temozolomide sensitivity both in vitro and in vivo, and a clinical case supported this finding. Mechanistically, we found that STAT3-induced HOXD-AS2 could interact with IGF2BP2 protein to upregulate STAT3 signaling, forming a positive feedback loop that regulates TMZ sensitivity in glioblastoma.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Shashank Pant, Qianyi Wu, Renae Ryan, Emad Tajkhorshid
Summary: EAATs, belonging to the SLC1A family of glutamate transporters, have been shown to activate chloride ion channels during transport. Molecular dynamics simulations in hEAAT1 reveal a chloride-conducting conformation, shedding light on the dual functionality of active transport and passive chloride permeation in human neurotransmitter transporters, a mechanism common across the SLC1A family.
ACS CHEMICAL NEUROSCIENCE
(2022)
Review
Neurosciences
Edoardo Agosti, Simona Serioli, Kanwaljeet Garg, Alberto Pietrantoni, Pietro Luigi Poliani, Marco Maria Fontanella
Summary: This study reported a rare case of multiple vertebral metastases from anal squamous cell carcinoma (SCC) and aimed to define a treatment strategy. Through case presentation and literature review, it was found that there is currently no universally accepted treatment strategy for vertebral metastases from anal SCC. Prompt and aggressive, local and systemic, and multimodal treatment of the vertebral lesions may be crucial for improving patient outcomes.
INTERNATIONAL JOURNAL OF NEUROSCIENCE
(2023)
Article
Clinical Neurology
Alberto Pietrantoni, Simona Serioli, Manuela Cominelli, Giovanni Lodoli, Roberto Stefini, Vincenzo Villanacci, Pietro Luigi Poliani
Summary: This article reports a rare case in which a patient was diagnosed with granulomatous hypophysitis, PitNET, and Crohn's disease, providing new evidence for the association between these diseases.
Article
Oncology
Valentina Pieri, Alberto L. Gallotti, Denise Drago, Manuela Cominelli, Ilaria Pagano, Valentina Conti, Silvia Valtorta, Angela Coliva, Sara Lago, Daniela Michelatti, Luca Massimino, Federica Ungaro, Laura Perani, Antonello Spinelli, Antonella Castellano, Andrea Falini, Alessio Zippo, Pietro L. Poliani, Rosa Maria Moresco, Annapaola Andolfo, Rossella Galli
Summary: Glioblastoma (GBM), a deadly brain tumor, has dysregulated metabolism that can be targeted for precise therapeutic strategies. Studying GBM sphere-forming cells, researchers identified the L-fucose pathway as a vulnerability specific to mesenchymal GBM, offering a potential precision medicine approach for targeting cancer metabolism.
Article
Radiology, Nuclear Medicine & Medical Imaging
Luisa Chiapparini, Valentina Opancina, Alessandra Erbetta, Bianca Pollo, Morgan Broggi, Elisa Ciceri
Summary: A 49-year-old man presented with right foot drop, bilateral cruralgia mainly on the left side, and genital and perianal hypoesthesia. Neurologic examination showed hypoesthesia in the L5 root region on the right side and right foot drop. Laboratory results showed abnormal levels of C-reactive protein, erythrocyte sedimentation rate, aspartate transaminase, alanine transaminase, lymphocytes, and neutrophils. CT and MRI of the lumbosacral spine were performed.
Article
Oncology
Aram Ko, Mohammad Hasanain, Young Taek Oh, Fulvio D'Angelo, Danika Sommer, Brulinda Frangaj, Suzanne Tran, Franck Bielle, Bianca Pollo, Rosina Paterra, Karima Mokhtari, Rajesh Kumar Soni, Matthieu Peyre, Marica Eoli, Laura Papi, Michel Kalamarides, Marc Sanson, Antonio Iavarone, Anna Lasorella
Summary: LZTR1 is a substrate-specific adaptor of a CUL3-dependent ubiquitin ligase frequently mutated in cancer. The study identified EGFR and AXL as LZTR1 substrates targeted for degradation, and found that LZTR1 mutations result in the accumulation and deregulated signaling of EGFR and AXL. The study also revealed vulnerabilities of LZTR1-mutant tumors to inhibition of EGFR and AXL, providing precision targeting for patients with LZTR1-mutant cancer.
Article
Medicine, General & Internal
Jacopo Falco, Emanuele Rubiu, Morgan Broggi, Mariangela Farinotti, Ignazio G. Vetrano, Marco Schiariti, Elena Anghileri, Marica Eoli, Bianca Pollo, Marco Moscatelli, Francesco Restelli, Elio Mazzapicchi, Emanuele La Corte, Giulio Bonomo, Marco Gemma, Giovanni Broggi, Paolo Ferroli, Francesco Acerbi
Summary: Maximizing surgical resection using fluorescein-guided surgery has been shown to improve overall survival in patients with glioblastoma. In this retrospective analysis, we evaluated the role of fluorescein-guided surgery in tumor resection, survival, and complications. The study results demonstrated a high rate of complete resection without any adverse effects related to fluorescein. The survival and progression-free survival were significantly improved compared to previous studies.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Oncology
Paolo Ferroli, Francesco Restelli, Giacomo Bertolini, Emanuele Monti, Jacopo Falco, Giulio Bonomo, Irene Tramacere, Bianca Pollo, Chiara Calatozzolo, Monica Patane, Silvia Schiavolin, Morgan Broggi, Francesco Acerbi, Alessandra Erbetta, Silvia Esposito, Elio Mazzapicchi, Emanuele La Corte, Ignazio Gaspare Vetrano, Giovanni Broggi, Marco Schiariti
Summary: This retrospective study analyzed the associations between possible prognostic factors and survival rate. Surgical resection, tumor volume, histological grade, extent of resection, and 3-month postoperative performance status were identified as important prognostic factors. Surgery for thalamic gliomas improves overall survival, and patients with stable performance status after 3 months have better prognosis. Therefore, accurate evaluation of predictors of 3-month postoperative performance status is crucial in deciding between biopsy or surgical removal.
Article
Oncology
Ana Belen Diaz Mendez, Andrea Sacconi, Elisa Tremante, Valentina Lulli, Valentina Caprara, Laura Rosano, Frauke Goeman, Mariantonia Carosi, Marta Di Giuliani, Giulia Vari, Antonio Silvani, Bianca Pollo, Carlo Garufi, Sara Ramponi, Giorgia Simonetti, Emilio Ciusani, Chiara Mandoj, Stefano Scalera, Veronica Villani, Agnese Po, Elisabetta Ferretti, Giulia Regazzo, Maria Giulia Rizzo
Summary: This study aimed to identify a microRNA signature as a non-invasive biomarker and investigate its impact on glioma biology. A three-microRNA signature was differentially expressed in the serum of glioma patients and correlated with patient survival. The signature negatively affects glioma functions and provides potential targets for therapeutic intervention.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Letter
Clinical Neurology
Elena Anghileri, Bianca Pollo, Cecilia Casali, Marcello Marchetti, Alessandra Erbetta
NEUROLOGICAL SCIENCES
(2023)
Article
Neurosciences
Roberto Liserre, Francesca Branzoli, Francesca Pagani, Magdalena Gryzik, Manuela Cominelli, Evelina Miele, Malgorzata Marjanska, Francesco Doglietto, Pietro Luigi Poliani
Summary: Medulloblastoma (MB) is a common malignant brain tumor in children and rarely found in adults. MB can be classified into four major molecular groups based on transcriptome profile. DNA methylation profiling has identified additional subgroups within these groups. This case report presents a rare occurrence of an adult MB with both non-canonical somatic IDH1(p.R132C) mutation and a GNAS mutation. Further genetic characterization of MB and the use of advanced medical imaging are important for understanding their biology and improving patient management. The findings raise the need for further investigations on therapeutic implications and prognostic relevance.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Review
Cell Biology
Gabriele Antonarelli, Valentina Pieri, Francesca Maria Porta, Nicola Fusco, Gaetano Finocchiaro, Giuseppe Curigliano, Carmen Criscitiello
Summary: Various tumors rely on post-translational modifications to promote invasiveness, angiogenesis, and reprogram cellular energetics. Fucosylation, a type of glycosylation, has been linked to immune and hormonal functions as well as tumor development. In breast cancer, fucosylation of the glycan core is associated with poor prognosis and increased metastatic potential. Pre-clinical studies have investigated the molecular mechanisms of core-fucosylation in breast cancer models and its potential as a biomarker for predicting cancer outcomes.
Review
Oncology
Giulio Bonomo, Alessandro Gans, Elio Mazzapicchi, Emanuele Rubiu, Paolo Alimonti, Marica Eoli, Rosina Paterra, Bianca Pollo, Guglielmo Iess, Francesco Restelli, Jacopo Falco, Francesco Acerbi, Marco Paolo Schiariti, Paolo Ferroli, Morgan Broggi
Summary: In this paper, the clinical and diagnostic features of Sporadic Spinal Psammomatous Malignant Melanotic Nerve Sheath Tumor (SSP-MMNST) are reviewed, and possible pathogenetic mechanisms are investigated to improve therapeutic strategies. A case of a young female with SSP-MMNST arising from C5-6 right spinal roots is also reported. The study found that SSP-MMNST has a high recurrence rate and residual disease is associated with a higher risk of systemic disease spreading, suggesting the importance of adjuvant radiation therapy.
FRONTIERS IN ONCOLOGY
(2023)
Article
Medicine, General & Internal
Matilde Taddei, Silvia Esposito, Gianluca Marucci, Alessandra Erbetta, Paolo Ferroli, Laura Grazia Valentini, Chiara Pantaleoni, Stefano D'Arrigo, Veronica Saletti, Bianca Pollo, Rosina Paterra, Daria Riva, Sara Bulgheroni
Summary: In this study, the cognitive and behavioral outcomes of children with low-grade CNS tumors treated with surgical intervention were analyzed retrospectively. The results showed that the sample had normal cognitive abilities and behavioral functioning, but weaknesses were observed in verbal working memory and processing speed. Factors such as younger age at symptoms' onset, glioneuronal histological type, cortical location with preoperative seizures, timing of surgery, and seizure control after surgery were found to be associated with cognitive and behavioral functioning. Timely treatment and regular assessment are important for the global outcome and daily functioning of these patients.
Letter
Clinical Neurology
Giacomo Sferruzza, Gaetano Finocchiaro
NEUROLOGICAL SCIENCES
(2023)