Article
Multidisciplinary Sciences
Sang S. Seo, Susana R. Louros, Natasha Anstey, Miguel A. Gonzalez-Lozano, Callista B. Harper, Nicholas C. Verity, Owen Dando, Sophie R. Thomson, Jennifer C. Darnell, Peter C. Kind, Ka Wan Li, Emily K. Osterweil
Summary: Dysregulated protein synthesis is a key contributing factor to the development of Fragile X syndrome. The authors of this study have identified a relationship between ribosome expression and the translation of long mRNAs, which is responsible for synaptic weakening in Fragile X syndrome.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Rohini Subrahmanyam, Deepanjali Dwivedi, Zubin Rashid, Katherine Bonnycastle, Michael A. Cousin, Sumantra Chattarji
Summary: This study reveals that FMRP represses spontaneous presynaptic SV fusion, while mGlu receptor activation increases this event, with reciprocal control likely mediated through their regulation of intrinsic neuronal excitability.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Neurosciences
Susana R. Louros, Sang S. Seo, Beatriz Maio, Cristina Martinez-Gonzalez, Miguel A. Gonzalez-Lozano, Melania Muscas, Nick C. Verity, Jimi C. Wills, Ka Wan Li, Matthew F. Nolan, Emily K. Osterweil
Summary: In fragile X syndrome, excessive neuronal protein synthesis is a core pathophysiology, but an overall increase in protein expression is not observed. Surprisingly, although protein degradation through the ubiquitin proteasome system (UPS) is significantly increased, this contributes to pathological changes. Normalizing proteasome activity corrects excessive protein synthesis and hyperactivation of neurons in response to auditory stimulation, reducing the incidence and severity of audiogenic seizures in the mouse model. Excessive activation of the UPS pathway in fragile X neurons can be targeted for therapeutic intervention.
Article
Cell Biology
Pawel Matulewicz, Arnau Ramos-Prats, Xavier Gomez-Santacana, Amadeu Llebaria, Francesco Ferraguti
Summary: This study aimed to assess the impact of mGlu(5) inactivation on neuronal oscillatory activity during fear retrieval in cued fear conditioned mice, showing that inhibition of mGlu(5) signaling decreased freezing behavior during fear retrieval and reduced theta rhythmic activity in both the mPFC and vHPC.
Article
Biochemistry & Molecular Biology
Madison Edwards, Simpson Joseph
Summary: Fragile X Syndrome and certain manifestations of autism spectrum disorder are caused by improper RNA regulation due to a deficiency of fragile X mental retardation protein (FMRP). Fragile X related proteins (FXPs) play a crucial role in mRNA regulation and potential mRNA targets. This study investigated the function of FXPs in translational control using three potential mRNA targets, analyzing the binding site(s) of FXPs within the mRNA and their impact on translation.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Vanessa Pereira, Juri Aparicio Arias, Amadeu Llebaria, Cyril Goudet
Summary: Neuropathic pain is a challenging condition to manage. In this study, the role of the amygdala in regulating neuropathic pain was investigated. The activation of mGlu4 receptors in the amygdala was found to alleviate sensory and depressive-like symptoms in a mouse model of neuropathy.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Carlos Alberto Castillo, Inmaculada Ballesteros-Yanez, David Agustin Leon-Navarro, Jose Luis Albasanz, Mairena Martin
Summary: The amyloid beta peptide plays a central role in Alzheimer's disease pathology. Exposure to A beta(25-35) in rat cortical neurons increased mGluR density and affinity, along with up-regulation of adenosine A(1)R and A(2A)R. The study highlights the possible involvement of metabotropic glutamate and adenosine receptors in the early events of AD physiopathology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Neurosciences
Ananth Prasad Burada, Rajesh Vinnakota, Bertrand Lambolez, Ludovic Tricoire, Janesh Kumar
Summary: Enigmatic orphan glutamate delta receptors (GluD) are a type of ionotropic glutamate receptors (iGluRs) that do not bind glutamate or evoke currents when binding glycine and D-serine. They are believed to function as structural proteins that facilitate synapse formation, maturation, and maintenance in the hippocampus and cerebellum. Recent research suggests that GluD receptors have interactions with metabotropic glutamate receptors (mGlus) and are gated by their activation, with new tools and structures helping to define their role in synaptic physiology.
Article
Reproductive Biology
Alexandra Spirkova, Veronika Kovarikova, Zuzana Sefcikova, Jozef Pisko, Martina Ksinanova, Juraj Koppel, Dusan Fabian, Stefan Cikos
Summary: The study reveals that glutamic acid can affect preimplantation embryo development through cell membrane receptors. High extracellular concentrations of glutamic acid can inhibit blastocyst development, which is of practical significance.
BIOLOGY OF REPRODUCTION
(2022)
Article
Cell Biology
Ji Geng, Tejinder Pal Khaket, Jie Pan, Wen Li, Yan Zhang, Yong Ping, Maria Inmaculada Cobos Sillero, Bingwei Lu
Summary: FMRP interacts with VDAC to regulate the formation and function of ERMCSs, which are critical for mito-Ca2+ homeostasis. Excessive ERMCS formation and ER-to-mitochondria Ca2+ transfer are observed in FXS. Inhibition of VDAC or other ERMCS components restores synaptic structure and function, rescues locomotion and cognitive deficits in FXS models.
DEVELOPMENTAL CELL
(2023)
Article
Biochemistry & Molecular Biology
James Robert Brasic, Ayon Nandi, David S. Russell, Danna Jennings, Olivier Barret, Samuel D. Martin, Keith Slifer, Thomas Sedlak, John P. Seibyl, Dean F. Wong, Dejan B. Budimirovic
Summary: Research suggests that dysfunction of the metabotropic glutamate receptor subtype 5 (mGluR(5)) plays a role in the pathogenesis of autism spectrum disorder (ASD). Contradictory findings about mGluR(5) expression in different subtypes of ASD have been reported. A study using a novel PET ligand found increased mGluR(5) expression in the cortical regions of participants with IASD, and reduced expression in all regions of men with FXS. This protocol shows promise as a valuable tool for measuring mGluR(5) expression in clinical trials for individuals with ASD and FXS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Elisa Donnard, Huan Shu, Manuel Garber
Summary: The study provides insights into the molecular and biological consequences of Fragile X syndrome (FXS), showing that neurons are the most impacted cell type and genes bound by FMRP are collectively decreased only in neurons. Additionally, metabolic pathways, such as translation and respiration, are upregulated in most cell types except excitatory neurons. These findings highlight the intricate interactions between different brain cell types and the potential for therapeutic interventions.
Review
Pharmacology & Pharmacy
Ananth Prasad Burada, Rajesh Vinnakota, Pratibha Bharti, Priyanka Dutta, Neelima Dubey, Janesh Kumar
Summary: GluD receptors are a subfamily of ionotropic glutamate receptors that play a crucial role in synapse formation, maturation, and maintenance of central nervous system functions. Despite the lack of knowledge about their endogenous ligands, significant discoveries have been made regarding their role in mediating trans-synaptic interactions and their unique non-swapped architecture. Additionally, the prospect of GluD ionotropic activity being regulated by direct interaction with metabotropic glutamate receptors is exciting.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Cell Biology
Sara G. Susco, Sulagna Ghosh, Patrizia Mazzucato, Gabriella Angelini, Amanda Beccard, Victor Barrera, Martin H. Berryer, Angelica Messana, Daisy Lam, Dane Z. Hazelbaker, Lindy E. Barrett
Summary: Down syndrome and fragile X syndrome may share underlying mechanisms, as evidenced by overlapping transcriptional perturbations and increased expression of select target proteins. Furthermore, upregulation of FMRP in Down syndrome patient cells can significantly reduce expression levels of candidate proteins and reverse global transcriptional perturbations.
Article
Biochemistry & Molecular Biology
Ekaterina V. Pershina, Irina Yu. Chernomorets, Dmitry A. Fedorov, Vladimir I. Arkhipov
Summary: In this study, the neuroprotective properties of the combination of memantine, a non-competitive NMDA receptor antagonist, and VU 0422288, a positive allosteric modulator of metabotropic glutamate receptors, were investigated. The results showed that the combined use of memantine and VU 0422288 significantly reduced neuronal cell death in the CA1 region of the hippocampus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Wangfa Zhao, Shih-Chieh Chuang, Steven R. Young, Riccardo Bianchi, Robert K. S. Wong
JOURNAL OF NEUROSCIENCE
(2015)
Article
Neurosciences
Clotilde Balucani, Riccardo Bianchi, Charles Ramkishun, Jeremy Weedon, Susan Law, Michael Szarek, Diana Rojas-Soto, Sara Tariq, Steven R. Levine
JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
(2015)
Article
Clinical Neurology
Clotilde Balucani, Riccardo Bianchi, Edward Feldmann, Jeremy Weedon, Dmitri Kolychev, Steven R. Levine
Article
Neurosciences
Clotilde Balucani, Riccardo Bianchi, Charles Ramkishun, Jeremy Weedon, Susan Law, Michael Szarek, Diana Rojas-Soto, Sara Tariq, Steven R. Levine
JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
(2015)
Article
Geriatrics & Gerontology
Syed F. Kazim, Shih-Chieh Chuang, Wangfa Zhao, Robert K. S. Wong, Riccardo Bianchi, Khalid Iqbal
FRONTIERS IN AGING NEUROSCIENCE
(2017)
Article
Clinical Neurology
Steven R. Levine, Sarah Z. Weingast, Jeremy Weedon, Dimitre G. Stefanov, Patricia Katz, Dana Hurley, Scott E. Kasner, Pooja Khatri, Joseph P. Broderick, James C. Grotta, Edward Feldmann, Peter D. Panagos, Jose G. Romano, Riccardo Bianchi, Brett C. Meyer, Phillip A. Scott, Doojin Kim, Clotilde Balucani
Article
Cell Biology
Ilham A. Muslimov, Aliya Tuzhilin, Thean Hock Tang, Robert K. S. Wong, Riccardo Bianchi, Henri Tiedge
JOURNAL OF CELL BIOLOGY
(2014)
Article
Neurosciences
Steven R. Young, Shih-Chieh Chuang, Wangfa Zhao, Robert K. S. Wong, Riccardo Bianchi
JOURNAL OF NEUROSCIENCE
(2013)
Article
Neurosciences
Emily K. Osterweil, Shih-Chieh Chuang, Alexander A. Chubykin, Michael Sidorov, Riccardo Bianchi, Robert K. S. Wong, Mark F. Bear
Article
Multidisciplinary Sciences
Syed Faraz Kazim, Julie Blanchard, Riccardo Bianchi, Khalid Iqbal
SCIENTIFIC REPORTS
(2017)
Review
Neurosciences
Syed Faraz Kazim, Joon Ho Seo, Riccardo Bianchi, Chloe S. Larson, Abhijeet Sharma, Robert K. S. Wong, Kirill Y. Gorbachev, Ana C. Pereira
Summary: Alzheimer's disease is the most common neurodegenerative disorder in the elderly, with recent evidence suggesting that network abnormalities may play a key role in cognitive decline. A beta and tau are implicated in inducing network hyperexcitability, with genetic mutations leading to increased A beta production and hyperphosphorylated tau accumulation associated with seizures and epilepsy in patients. This review discusses the common and distinct roles of tau and A beta in neuronal hyperexcitability in Alzheimer's disease, proposing hypotheses for future experiments.
Article
Emergency Medicine
Benjamin H. Schnapp, Al'ai Alvarez, Riccardo Bianchi, Holly Caretta-Weyer, Corlin Jewell, Annahieta Kalantari, Eric Lee, Danielle Miller, Antonia Quinn
Summary: For residency recruitment, transparency with selection criteria, holistic application review, standardized letters of evaluation, and blinding applicant files for interviewers are considered some of the best practices.
AEM EDUCATION AND TRAINING
(2021)
Meeting Abstract
Clinical Neurology
Clotilde Balucani, Sarah Z. Weingast, Jeremy Weedon, Dimitre G. Stefanov, Patricia Katz, Dana Hurley, Pooja Khatri, Joseph P. Broderick, Scott E. Kasner, James C. Grotta, Edward Feldmann, Peter D. Panagos, Jose G. Romano, Riccardo Bianchi, Brett C. Meyer, Phillip A. Scott, Doojin Kim, Steven R. Levine
Meeting Abstract
Clinical Neurology
Clotilde Balucani, Riccardo Bianchi, Jeremy Weedon, Steven Levine
Review
Medicine, General & Internal
Mario Ciampolini, H. David Lovell-Smith, Timothy Kenealy, Riccardo Bianchi
INTERNATIONAL JOURNAL OF GENERAL MEDICINE
(2013)