Article
Physics, Fluids & Plasmas
Paul C. Bressloff
Summary: In this paper, the relaxation to steady state of intracellular diffusion in a pair of cells with gap junction coupling is analyzed. The local accumulation time is calculated and it is found to be a monotonically increasing function of spatial position. Both static and dynamic gap junction models are considered.
Review
Neurosciences
Magdalena Pereyra, Jorge H. Medina
Summary: Retrieval is a highly regulated and dynamic phase in memory processing, where AMPA receptors play a crucial role in supporting transient memory trace reactivation. The dynamic movements and changes in receptor number and subunit composition of AMPAR during retrieval greatly impact memory recall through their differential regulations in plasticity processes.
FRONTIERS IN HUMAN NEUROSCIENCE
(2021)
Article
Neurosciences
Magdalena Pereyra, Ana Belen de Landeta, Juliana Fatima Dalto, Cynthia Katche, Jorge H. Medina
Summary: The study shows that the activity of mTORC1 signaling pathway is crucial for the normal expression of aversive and non-aversive long-term memories during memory retrieval. Specifically, the de novo synthesis of GluA1 and GluA2 AMPAR subunits plays an important role in memory retrieval, with mTORC1 potentially regulating AMPAR trafficking during this process.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Miranda Mele, Pasqualino De Luca, Ana Rita Santos, Marta Vieira, Ivan L. Salazar, Paulo S. Pinheiro, Carlos B. Duarte
Summary: This study investigated the regulation of the synaptic protein GRASP1 by ubiquitin-dependent mechanisms, revealing an impact on the surface distribution and activity of AMPA receptors. Ubiquitination was found to decrease dendritic levels of GRASP1 and surface expression of GluA1 subunits, leading to a reduction in mEPSC amplitudes, effects that were partially reversed by cotransfection with GRASP1.
Article
Neurosciences
Yao Q. Wang, Yanhua H. Huang, Saju Balakrishnan, Lidong Liu, Yu Tian Wang, Eric J. Nestler, Oliver M. Schluter, Yan Dong
Summary: This study elucidates the dynamic interactions between AMPARs and NMDARs during the generation and maturation of silent synapses in the NAc after cocaine experience. The findings provide a mechanistic basis for manipulating new synaptic contacts and potentially new neural network patterns created by these synapses for therapeutic benefit.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Longfei Cheng, Keen Chen, Jiong Li, Jiaming Wu, Jiaqi Zhang, Li Chen, Guoqing Guo, Jifeng Zhang
Summary: CRMP2 can promote the surface expression of AMPA receptor GluA1 subunit in hippocampal neurons and in HEK293T cells expressing GluA1 subunits, through interaction with GluA1 and regulation by Cdk5 phosphorylation.
MOLECULAR NEUROBIOLOGY
(2022)
Review
Neurosciences
Jeremy M. Henley, Jithin D. Nair, Richard Seager, Busra P. Yucel, Gavin Woodhall, Benjamin S. Henley, Karolina Talandyte, Hope I. Needs, Kevin A. Wilkinson
Summary: Epilepsy is caused by abnormal neuronal network activity. The review focuses on the role and regulation of kainate and AMPA receptors in seizure activity, discussing the impact of GluK2 and GluA2 subunits on their respective receptors' properties.
Article
Neurosciences
Thomas P. Cast, Daniel J. Boesch, Kim Smyth, Alisa E. Shaw, Michael Ghebrial, Soham Chanda
Summary: The amino acid substitution mutation (R101Q) in the NLGN4 gene impairs the maturation and surface trafficking of NLGN4 protein, leading to reduced synaptic localization and functional impact on neurons.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Neurosciences
Robert F. Niescier, Yu-Chih Lin
Summary: Autism Spectrum Disorder (ASD) is a multifaceted condition associated with difficulties in social interaction and communication. Intensive research has revealed an association with a large number and variety of low-penetrance genes. Genes associated with neurodevelopmental conditions that share the autism comorbidity include Fragile X syndrome, Rett Syndrome, and Tuberous Sclerosis.
Article
Neurosciences
Peter M. Matthews, Alexandra Pinggera, Domen Kampjut, Ingo H. Greger
Summary: AMP-type glutamate receptors in the central nervous system are predominantly involved in excitatory synaptic transmission, with their signaling properties and abundance at synapses being crucial for synapse efficacy and plasticity. Unique to these receptors is the presence of interacting proteins that play a role in their complex regulation, including transient interactions with the receptor cytoplasmic tail and the N-terminal domain. Additionally, an array of transmembrane proteins act as auxiliary subunits impacting receptor trafficking, stabilization, gating, and pharmacology.
Article
Neurosciences
Joyce Keifer
Summary: An in vitro model was used to investigate the synaptic plasticity mechanisms underlying the acquisition of associative learning. The model replaced real stimuli with patterned stimulation of cranial nerves using an isolated turtle brainstem preparation. The primary findings demonstrated the cellular and molecular mechanisms involved in learning acquisition. It was shown that the intact cerebellum was not necessary for the acquisition of conditioned responses (CRs), but the appropriate timing was crucial. Synaptic mechanisms involving AMPA receptor (AMPAR) trafficking were found to play a role, regulated by specific signal transduction cascades and guided by protein chaperones. The expression of the brain-derived neurotrophic factor (BDNF) protein was central to AMPAR trafficking and conditioning, regulated by epigenetic mechanisms. A hypothesis was proposed suggesting that learning genes like BDNF are poised for rapid activation or repression in response to environmental stimuli through chromatin modifications. These in vitro studies have greatly contributed to our understanding of the cellular and molecular mechanisms underlying associative learning.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jing Song, Ting Gao, Wenjing Li, Chunman Yuan, Jiarui Hao, Xinyu Xia
Summary: Aluminum inhibits the trafficking of AMPA receptors through its effect on the palmitoylation/depalmitoylation cycle. Decreased palmitoylation levels of AMPA receptors may be a mechanism of Al action.
BIOLOGICAL TRACE ELEMENT RESEARCH
(2023)
Article
Neurosciences
Shu-Ling Chiu, Chih-Ming Chen, Richard L. Huganir
Summary: The study revealed a novel function of ICA69 in AMPAR trafficking, synaptic plasticity, and animal cognition. ICA69 regulates the distribution and stability of PICK1 in neurons, which impacts AMPAR function in the brain. The genetic deletion of ICA69 selectively impairs NMDAR-dependent LTP and leads to behavioral deficits in spatial and associative learning and memory.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Clinical Neurology
Wei Zhang, Ming Lei, Qianwen Wen, Dunke Zhang, Guangcheng Qin, Jiying Zhou, Lixue Chen
Summary: This study investigated the role of the dopamine D2 receptor in chronic migraine and its effect on GLUA1-containing AMPA receptor trafficking. The results suggest that the dopamine D2 receptor can modulate the trafficking of GLUA1-containing AMPA receptors through the PI3K signaling pathway and have an impact on central sensitization.
JOURNAL OF HEADACHE AND PAIN
(2022)
Article
Cell Biology
Rabia R. Khawaja, Amit Agarwal, Masahiro Fukaya, Hey-Kyeong Jeong, Scott Gross, Estibaliz Gonzalez-Fernandez, Jonathan Soboloff, Dwight E. Bergles, Shin H. Kang
Summary: Regulation of AMPAR GluA2 content in oligodendrocyte precursor cells affects cell proliferation and regenerative behavior, serving as a potential target for myelin repair.
Article
Clinical Neurology
Ghil Schwarz, Gargi Banerjee, Isabel C. Hostettler, Gareth Ambler, David J. Seiffge, Hatice Ozkan, Simone Browning, Robert Simister, Duncan Wilson, Hannah Cohen, Tarek Yousry, Rustam Al-Shahi Salman, Gregory Y. H. Lip, Martin M. Brown, Keith W. Muir, Henry Houlden, Rolf Jager, David J. Werring
Summary: This study found associations between putative biomarkers of parenchymal CAA and putative biomarkers of leptomeningeal CAA, and suggested that CT biomarkers may help in diagnosing CAA, but MRI still plays an important role in ICH survivors with suspected CAA.
INTERNATIONAL JOURNAL OF STROKE
(2023)
Review
Clinical Neurology
Francesca Magrinelli, Kailash P. Bhatia, Mehran Beiraghi Toosi, Fatemeh Arab, Ehsan Ghayoor Karimiani, Sahar Sedighzadeh, Behnaz Ansari, Maedeh Neshatdoust, Clarissa Rocca, Henry Houlden, Reza Maroofian
Summary: This article reports a new phenotype of childhood-onset choreo-dystonia in four patients from two unrelated Iranian pedigrees, who harbor a novel pathogenic variant in the HPCA gene. A systematic review of the literature reveals that HPCA-related dystonia can present as an isolated condition or in combination with various symptoms. Most cases show a poor or no response to common antidystonic medications.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Clinical Neurology
Vincenzo Salpietro, Valentina Galassi Deforie, Stephanie Efthymiou, Emer O'Connor, Anna Marce-Grau, Reza Maroofian, Pasquale Striano, Federico Zara, Michelle M. Morrow, Adi Reich, Amy Blevins, Julia Sala-Coromina, Andrea Accogli, Sara Fortuna, Marie Alesandrini, P. Y. Billie Au, Nilika Shah Singhal, Benjamin Cogne, Bertrand Isidor, Michael G. Hanna, Alfons Macaya, Dimitri M. Kullmann, Henry Houlden, Roope Mannikko
Summary: Novel mutations in KCNA6 gene were found to be associated with early infantile epileptic phenotypes and neurodevelopmental anomalies. Functional characterization revealed that these mutations affect channel closure and voltage dependence. This study is the first to report the association between de novo variants in KCNA6 and neurological features.
Article
Clinical Neurology
Zhongbo Chen, Arianna Tucci, Valentina Cipriani, Emil K. Gustavsson, Kristina Ibanez, Regina H. Reynolds, David Zhang, Letizia Vestito, Alejandro Cisterna Garcia, Siddharth Sethi, Jonathan W. Brenton, Sonia Garcia-Ruiz, Aine Fairbrother-Browne, Ana-Luisa Gil-Martinez, Nick Wood, John A. Hardy, Damian Smedley, Henry Houlden, Juan Botia, Mina Ryten
Summary: Using a systems biology approach, Chen et al. found that genes associated with adult- and child-onset ataxia share common characteristics, including a high density of short tandem repeats. Removing the age-of-onset partition and screening for repeat expansions could improve the diagnosis of hereditary ataxia.
Article
Clinical Neurology
Vinojini Vivekanandam, Rebecca Ellmers, Dipa Jayaseelan, Henry Houlden, Roope Mannikko, Michael G. Hanna
Summary: Accurately determining the pathogenicity of uncertain missense genetic variants is a challenge for clinical use of genetic data. In this study, nine in silico predictive tools were compared with cell-based electrophysiology for CLCN1 variants related to myotonia congenita. Most tools showed poor accuracy, with MutationTaster and REVEL having the highest accuracy but poor specificity. Combining methods improved overall performance but lacked specificity. The current predictive tools for this chloride channel are unreliable, and better tools are urgently needed. Improving predictive tool accuracy is a wider challenge for genetic data implementation.
Article
Genetics & Heredity
Elisa Cali, Mohnish Suri, Marcello Scala, Matteo P. Ferla, Shahryar Alavi, Eissa Ali Faqeih, Emilia K. Bijlsma, Kristen M. Wigby, Diana Baralle, Mohammad Y. Mehrjardi, Jennifer Schwab, Konrad Platzer, Katharina Steindl, Mais Hashem, Marilyn Jones, Dmitriy M. Niyazov, Jennifer Jacober, Rebecca Okashah Littlejohn, Denisa Weis, Neda Zadeh, Lance Rodan, Alice Goldenberg, Francois Lecoquierre, Marina Dutra-Clarke, Gabriella Horvath, Dana Young, Naama Orenstein, Shahad Bawazeer, Anneke T. Vulto-van Silfhout, Yvan Herenger, Mohammadreza Dehghani, Seyed Mohammad Seyedhassani, Amir Bahreini, Mahya E. Nasab, A. Gulhan Ercan-Sencicek, Zahra Firoozfar, Mojtaba Movahedinia, Stephanie Efthymiou, Pasquale Striano, Ehsan Ghayoor Karimiani, Vincenzo Salpietro, Jenny C. Taylor, Melody Redman, Alexander P. A. Stegmann, Andreas Laner, Ghada Abdel-Salam, Megan Li, Mario Bengala, Amelie Johanna Muller, Maria C. Digilio, Anita Rauch, Murat Gunel, Hannah Titheradge, Daniela N. Schweitzer, Alison Kraus, Irene Valenzuela, Scott D. McLean, Chanika Phornphutkul, Mustafa Salih, Amber Begtrup, Rhonda E. Schnur, Erin Torti, Tobias B. Haack, Carlos E. Prada, Fowzan S. Alkuraya, Henry Houlden, Reza Maroofian
Summary: PRMT7-related syndrome is a neurodevelopmental disorder characterized by short stature, intellectual developmental disability, hypotonia, brachydactyly, and distinct facial morphology. This study provides a comprehensive description of the clinical characteristics of this syndrome, contributing to a better understanding of the disease.
GENETICS IN MEDICINE
(2023)
Article
Genetics & Heredity
Heba Morsy, Mehdi Benkirane, Elisa Cali, Clarissa Rocca, Kristina Zhelcheska, Valentina Cipriani, Evangelia Galanaki, Reza Maroofian, Stephanie Efthymiou, David Murphy, Mary O'Driscoll, Mohnish Suri, Siddharth Banka, Jill Clayton-Smith, Thomas Wright, Melody Redman, Jennifer A. Bassetti, Mathilde Nizon, Benjamin Cogne, Rami Abu Jamra, Tobias Bartolomaeus, Marion Heruth, Ilona Krey, Janina Gburek-Augustat, Dagmar Wieczorek, Felix Gattermann, Meriel Mcentagart, Alice Goldenberg, Lucie Guyant-Marechal, Hector Garcia-Moreno, Paola Giunti, Brigitte Chabrol, Severine Bacrot, Roger Buissonniere, Virginie Magry, Vykuntaraju K. Gowda, Varunvenkat M. Srinivasan, Bela Melegh, Andras Szabo, Katalin Sumegi, Mireille Cossee, Monica Ziff, Russell Butterfield, David Hunt, Georgina Bird-Lieberman, Michael Hanna, Michel Koenig, Michael Stankewich, Jana Vandrovcova, Henry Houlden
Summary: The purpose of this study was to understand the phenotypic spectrum of SPTAN1 variants. It was found that SPTAN1 variants were significantly enriched in families with hereditary ataxia or hereditary spastic paraplegia. A total of 31 individuals with SPTAN1 variants were identified, with 10 patients presenting with pure or complex HSP/HA and the remaining 21 patients having developmental delay and seizures. Fibroblasts derived from two patients showed irregular alpha II-spectrin aggregation.
GENETICS IN MEDICINE
(2023)
Article
Genetics & Heredity
Ella F. Whittle, Madison Chilian, Ehsan Ghayoor Karimiani, Helga Progri, Daniela Buhas, Melis Kose, Rebecca D. Ganetzky, Mehran Beiraghi Toosi, Paria Najarzadeh Torbati, Reza Shervin Badv, Ivan Shelihan, Hui Yang, Houda Zghal Elloumi, Sukyeong Lee, Yalda Jamshidi, Alan M. Pittman, Henry Houlden, Erika Ignatius, Shamima Rahman, Reza Maroofian, Wan Hee Yoon, Christopher J. Carrol
Summary: This study aimed to identify the genetic cause of a novel autosomal recessive neurodevelopmental disorder characterized by global developmental delay, movement disorder, and metabolic abnormalities. Through clinical characterization and genetic analysis, the researchers identified three novel homozygous variants in the OGDH gene. Functional studies demonstrated that these variants interfered with the structure and function of the OGDH protein, leading to the observed neurodevelopmental disorder. This research highlights the importance of studying genetic causes of neurodevelopmental disorders for understanding their underlying mechanisms and developing targeted therapies.
GENETICS IN MEDICINE
(2023)
Article
Oncology
Mohamed E. Elsesy, Su Jung Oh-Hohenhorst, Christoph Oing, Alicia Eckhardt, Susanne Burdak-Rothkamm, Malik Alawi, Christian Mueller, Ulrich Schueller, Tobias Maurer, Gunhild von Amsberg, Cordula Petersen, Kai Rothkamm, Wael Y. Mansour
Summary: This study provides preclinical models for castration-resistant prostate cancer (CRPC) that can predict homologous recombination repair (HRR) defects and the sensitivity to olaparib and cisplatin. These models recapitulate the features of primary tumors, enabling individualized drug screening for tailored therapy recommendations.
MOLECULAR ONCOLOGY
(2023)
Editorial Material
Pediatrics
Stephanie Lorenz, Ilona Krey, Frederike Harms, Anja Freiseis, Florian Schmid, Roman Pokora, Kristina Stamos, Daniela Kohlfuerst, Anne Sophie Albertowski
Summary: Climate change is a silent crisis and the biggest threat of our times. It has negative impacts on both physical and mental health, particularly for children and adolescents. To address this crisis, politicians, healthcare professionals, and society as a whole need to take urgent and extensive actions to protect the well-being of future generations.
MONATSSCHRIFT KINDERHEILKUNDE
(2023)
Review
Genetics & Heredity
Ibrahim M. Abdelrazek, Tess Holling, Frederike L. Harms, Malik Alawi, Tarek Omar, Ebtesam Abdalla, Kerstin Kutsche
Summary: This article reports two cases of Egyptian patients with a phenotype suggestive of craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome-1 (CFSMR1). Both patients carried a homozygous TMCO1 variant and exhibited some rare clinical features such as hearing loss and syndactyly. Analysis of previously reported patients revealed different TMCO1 variants. It was found that TMCO1 may play important roles in Ca2+ channels and mitochondria, and the heterodimerization of TMCO1 and RAB5IF/C20orf24 may explain the pathophysiological role of ER-mitochondria interaction in CFSMR.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2023)
Article
Developmental Biology
Wahid Ullah, Muhammad Ilyas, Muhammad Tariq, Maria Imdad, Ikram Ullah, Stephanie Efthymiou, Muhammad Faheem, Muhammad Abbas, Muhammad Aamir, Muhammad Nouman, Henry Houlden, S. Y. N. A. P. S. Study Group SYNAPS Study Group
Summary: This study identified the genetic basis of WARBM syndrome in a Pashtun family from Pakistan. MRI analysis showed cerebral atrophy and exome sequencing identified a novel variant in the RAB3GAP1 gene. This rare variant expands the mutation spectrum of Micro syndrome.
INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE
(2023)
Article
Neurosciences
Zhongbo Chen, Regina H. Reynolds, Antonio F. Pardinas, Sarah A. Gagliano Taliun, Wouter van Rheenen, Kuang Lin, Aleksey Shatunov, Emil K. Gustavsson, Isabella Fogh, Ashley R. Jones, Wim Robberecht, Philippe Corcia, Adriano Chio, Pamela J. Shaw, Karen E. Morrison, Jan H. Veldink, Leonard H. van den Berg, Christopher E. Shaw, John F. Powell, Vincenzo Silani, John A. Hardy, Henry Houlden, Michael J. Owen, Martin R. Turner, Mina Ryten, Ammar Al-Chalabi
Summary: This study found that Neanderthal DNA introgression does not contribute to the genetic risk of neurodegenerative disorders in anatomically-modern humans. Additionally, there is no evidence to support the idea that common variants associated with these disorders are maintained by natural selection. These findings provide valuable insights into the origins of neurodegenerative diseases and address longstanding debates.
NEUROBIOLOGY OF DISEASE
(2023)
Review
Clinical Neurology
Yee Yen Goh, Emma Saunders, Samantha Pavey, Emma Rushton, Niall Quinn, Henry Houlden, Viorica Chelban
Summary: This article is a practical guide to diagnosing and managing multiple system atrophy (MSA). It explains the newly published Movement Disorders Society Consensus Diagnostic Criteria, which aim to reduce time to diagnosis. The key clinical features of MSA are highlighted to aid in diagnosis. The article also discusses practical symptom management and improving quality of life for people with MSA.
PRACTICAL NEUROLOGY
(2023)
Article
Genetics & Heredity
Laura Hecher, Frederike L. L. Harms, Jasmin Lisfeld, Malik Alawi, Jonas Denecke, Kerstin Kutsche
Summary: Type I inositol polyphosphate-4-phosphatase (INPP4A) controls cell proliferation, apoptosis, and endosome function. Mutations in INPP4A can cause neurodevelopmental disorders. We report a girl with a novel homozygous INPP4A variant and determine the subcellular distributions of different INPP4A isoforms. Our data suggests the important function of INPP4A isoforms in the brain.