Article
Cell Biology
Jaiprakash Sharma, Shalaka Mulherkar, Uan- Chen, Yan Xiong, Lakshya Bajaj, Byoung-Kyu Cho, Young Ah Goo, Hon-Chiu Eastwood Leung, Kimberley F. Tolias, Marco Sardiello
Summary: This study discovered that the cytosolic protein KCTD7, in complex with Cullin-3 and Rbx1, regulates calpain activity through non-degradative ubiquitination, and loss of this ubiquitination leads to neurodegenerative diseases. The study also found that Cullin-3-KCTD7 mediates ubiquitination of all ubiquitous calpains. These findings unveil a novel mechanism and potential therapeutic target to restrain calpain activity and shed light on the molecular pathogenesis of KCTD7-associated disease.
Article
Clinical Neurology
Arunan Selvarajah, Carolina Gorodetsky, Paula Marques, Quratulain Zulfiqar Ali, Anne T. Berg, Alfonso Fasano, Danielle M. Andrade
Summary: Limited information is available about Dravet syndrome (DS) in adults compared to the pediatric population. This study aimed to examine gait and motor manifestations in adults with DS. The findings revealed that motor symptoms and gait worsen progressively as patients with DS age.
Article
Clinical Neurology
Jenna C. Carpenter, Roope Mannikko, Catherine Heffner, Jana Heneine, Marisol Sampedro-Castaneda, Gabriele Lignani, Stephanie Schorge
Summary: Mutations in KCNC1 can cause MEAK, characterized by reduced neuronal excitability and morphological abnormalities, indicating an important role of K(V)3.1 channels in neuronal development.
Review
Developmental Biology
Sima Binaafar, Masoud Garshasbi, Ali Reza Tavasoli, Reza Shervin Badv, Seyyed Mohammad Mahdi Hosseiny, Debopam Samanta, Bahareh Rabbani, Nejat Mahdieh
Summary: The study focused on patients with nonsyndromic early-onset epileptic encephalopathy (NSEOEE) and reported 2 novel cases from Iran. Through genetic and phenotypic analysis, significant impact of KCTD7 gene mutations on NSEOEE was identified, emphasizing the importance of careful consideration in data analysis. The study also highlighted the diverse geographical distribution and potential therapeutic opportunities for KCTD7-related NSEOEE.
DEVELOPMENTAL NEUROSCIENCE
(2021)
Article
Neurosciences
Priyanka Sinha, Bhupender Verma, Subramaniam Ganesh
Summary: Brain aging is characterized by a decline in cellular homeostatic processes, leading to a decreased ability to respond to physiological stress. The aged brain shows physical changes such as degenerating neurons, proteinaceous plaques and tangles, intracellular deposition of glycogen, and elevated neuroinflammation, which are also seen in neurodegenerative disorders. In this study, the authors demonstrate that the expression level of genes implicated in progressive myoclonus epilepsy (PME) decreases with age, resulting in compromised neuronal response and increased susceptibility to seizures. Furthermore, they show that suppressing neuroinflammation can improve seizure susceptibility in both aged animals and animal models of PME.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Clinical Neurology
Cinzia Costa, Karen L. Oliver, Carmen Calvello, Jillian M. Cameron, Valentina Imperatore, Laura Tonelli, Davide Colavito, Silvana Franceschetti, Laura Canafoglia, Samuel F. Berkovic, Paolo Prontera
Summary: Progressive myoclonus epilepsies (PMEs) are a diverse group of neurodegenerative disorders that typically occur in late childhood. Through genome-wide molecular studies, pathogenic variants in the IRF2BPL gene were identified in patients with PME, suggesting its involvement in the disease. These findings expand the phenotypic spectrum of IRF2BPL-related disorders and highlight the importance of considering this gene in the diagnosis of patients with PME.
Review
Neurosciences
Sara Bernardi, Federica Gemignani, Maria Marchese
Summary: Progressive myoclonic epilepsies (PMEs) are rare neurodegenerative diseases characterized by myoclonus, seizures, and neurological deterioration. The involvement of the cerebellar cortex and the loss of Purkinje cells (PCs) in PMEs are associated with motor impairments and epilepsy. This review focuses on the role of PCs in epilepsy and particularly highlights their involvement in seizure phenotype in neuronal ceroid lipofuscinosis (NCL).
NEUROBIOLOGY OF DISEASE
(2023)
Article
Neurosciences
Tracy S. Gertler, Suraj Cherian, Jean-Marc Dekeyser, Jennifer A. Kearney, Alfred L. George
Summary: Pathogenic variants in KCNT1 gene are associated with intractable epilepsy and may drive the development of epilepsy through alterations in inhibitory signaling and neuronal excitability.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Clinical Neurology
Nina E. Ottosson, Malin Silvera Ejneby, Xiongyu Wu, Argel Estrada-Mondragon, Michelle Nilsson, Urban Karlsson, Melanie Schupp, Salome Rognant, Thomas Andrew Jepps, Peter Konradsson, Fredrik Elinder
Summary: Resin acid derivatives have been found to activate the hK(V)7.2/7.3 channel, showing potential for epilepsy treatment and demonstrating significant antiseizure effects in animal studies. These compounds act on the channel in a unique way compared to existing drugs, and have fewer side effects.
Review
Clinical Neurology
Giovanni Assenza, Cristofaro Nocerino, Mario Tombini, Giancarlo Di Gennaro, Alfredo D'Aniello, Alberto Verrotti, Alfonso Marrelli, Lorenzo Ricci, Jacopo Lanzone, Vincenzo Di Lazzaro, Leonilda Bilo, Antonietta Coppola
Summary: Perampanel showed significant improvement in symptoms of PMEs patients, particularly in myoclonus, disability, and seizures, with the best response seen in individuals with Unverricht-Lundborg disease. While no prospective trials were found, a systematic review revealed that the majority of patients had positive responses to perampanel.
FRONTIERS IN NEUROLOGY
(2021)
Article
Clinical Neurology
Sophie F. Hill, Julie M. Ziobro, Paymaan Jafar-Nejad, Frank Rigo, Miriam H. Meisler
Summary: Voltage-gated sodium and potassium channels play a crucial role in regulating neuronal action potentials, and mutations in these channels can lead to seizure disorders. This study demonstrates that reducing the expression of Scn8a can compensate for loss-of-function mutations in Kcna1 and Kcnq2, providing a potential therapeutic approach for genetic epilepsies caused by mutations in potassium channel genes.
Letter
Clinical Neurology
Jinhee Kim, Ilsoo Kim, Seong-Beom Koh
Summary: A novel variant of DHDDS mutation was reported in a patient with progressive adult-onset myoclonus ataxia. The mutation in this patient differed from previous reports of denovo mutations in DHDDS in 6 patients who exhibited tremor-like myoclonus and generalized epilepsy.
PARKINSONISM & RELATED DISORDERS
(2021)
Article
Multidisciplinary Sciences
Quentin Plumereau, Aya Ebdalla, Hugo Poulin, Juan Pablo Appendino, Morris H. Scantlebury, Ping Yee Billie Au, Mohamed Chahine
Summary: In this study, a functional test was conducted to assess the effects of a SCN1A gene mutation on epilepsy, and it was found that a specific mutation led to the inability of the Na(V)1.1 channel to produce functional Na+ currents, possibly due to a pore defect in the channel. This study highlights the importance of functional testing in understanding the pathophysiology and potential treatment decisions for epilepsy.
SCIENTIFIC REPORTS
(2022)
Review
Genetics & Heredity
Yirao Chen, Xingyan Yang, Xinxiang Yan, Lu Shen, Jifeng Guo, Qian Xu
Summary: This study presents a case of adult-onset progressive myoclonic epilepsy-11 (EPM-11) caused by a novel SEMA6B variant. The patient exhibited gait instability, seizures, and cognitive impairment. This case sheds light on the phenotypic and genotypic profiles of EPM-11 and emphasizes the need for further functional studies to understand its pathogenesis.
FRONTIERS IN GENETICS
(2023)
Article
Clinical Neurology
Jayant N. N. Acharya, Vinita J. J. Acharya
Summary: Myoclonus can be divided into epileptic and nonepileptic types. Juvenile myoclonic epilepsy (JME) is a common idiopathic generalized epilepsy with characteristic myoclonic, tonic-clonic, and absence seizures. Recent studies have shown neurological and imaging abnormalities in the frontal lobes and thalamus of JME patients. Progressive myoclonic epilepsy is a distinct syndrome with various specific causes and can be challenging to differentiate from JME or misdiagnosed as drug-resistant JME. Neurophysiological tests can help distinguish between JME and progressive myoclonic epilepsy, as well as different forms of progressive myoclonic epilepsy (EPM1 and EPM2).
JOURNAL OF CLINICAL NEUROPHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Daniel L. Polla, Elisa Rahikkala, Michaela K. Bode, Tuomo Maatta, Teppo Varilo, Thyrza Loman, Anju K. Philips, Mitja Kurki, Aarno Palotie, Jarmo Korkko, Kristiina Avela, Valerie Jacquemin, Isabelle Pirson, Marc Abramowicz, Arjan P. M. de Brouwer, Outi Kuismin, Hans van Bokhoven, Irma Jarvela
EUROPEAN JOURNAL OF HUMAN GENETICS
(2019)
Letter
Genetics & Heredity
Aurore Tourville, Christelle Michiels, Christel Condroyer, Audrey Meunier, Monique Cordonnier, Jose-Alain Sahel, Isabelle Audo, Marc Abramowicz, Christina Zeitz
OPHTHALMIC GENETICS
(2019)
Correction
Biochemistry & Molecular Biology
Daniel L. Polla, Elisa Rahikkala, Michaela K. Bode, Tuomo Maatta, Teppo Varilo, Thyrza Loman, Anju K. Philips, Mitja Kurki, Aarno Palotie, Jarmo Korkko, Paivi Vieira, Kristiina Avela, Valerie Jacquemin, Isabelle Pirson, Marc Abramowicz, Arjan P. M. de Brouwer, Outi Kuismin, Hans van Bokhoven, Irma Jarvela
EUROPEAN JOURNAL OF HUMAN GENETICS
(2020)
Article
Neurosciences
Adeline Gazan, Daniel Rial, Serge N. Schiffmann
EUROPEAN JOURNAL OF NEUROSCIENCE
(2020)
Article
Genetics & Heredity
Sarah Duerinckx, Valerie Jacquemin, Severine Drunat, Yoann Vial, Sandrine Passemard, Camille Perazzolo, Annick Massart, Julie Soblet, Judith Racape, Laurence Desmyter, Cindy Badoer, Sofia Papadimitriou, Yann-Ael Le Borgne, Anne Lefort, Frederick Libert, Viviane De Maertelaer, Marianne Rooman, Sabine Costagliola, Alain Verloes, Tom Lenaerts, Isabelle Pirson, Marc Abramowicz
Article
Biochemistry & Molecular Biology
Bertille Montibus, Jil Cercy, Tristan Bouschet, Amandine Charras, Stephanie Maupetit-Mehouas, David Nury, Celine Gonthier-Gueret, Sabine Chauveau, Nicolas Allegre, Caroline Chariau, Charles C. Hong, Isabelle Vaillant, C. Joana Marques, Franck Court, Philippe Arnaud
Summary: The induction of Kdm6b expression upon neural commitment of mouse embryonic stem cells is linked to rearrangement between two 3D configurations defined by the promoter contact with different regions in the Kdm6b locus. This rearrangement is associated with changes in 5-hydroxymethylcytosine (5hmC) levels and requires the functional ten-eleven-translocation (TET) 3 protein. This reveals an unexpected interplay between the 5-hmC and H3K27me3 pathways during neural lineage commitment in mammals.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Neurosciences
Daniel Rial, Emma Puighermanal, Marine Chazalon, Emmanuel Valjent, Serge N. Schiffmann, Alban de Kerchove d'Exaerde
BIOLOGICAL PSYCHIATRY
(2020)
Article
Immunology
Ghadeer AbdulHussain, Fawaz Azizieh, Ma'asoumah Makhseed, Raj Raghupathy
JOURNAL OF REPRODUCTIVE IMMUNOLOGY
(2020)
Article
Immunology
Osama Kassem, Abdulwahab Al-Saleh, Fawaz Azizieh, Kamaludin Dingle
JOURNAL OF INFLAMMATION RESEARCH
(2020)
Article
Neurosciences
Stefan Pommer, Yumiko Akamine, Serge N. Schiffmann, Alban de Kerchove D'Exaerde, Jeffery R. Wickens
Summary: Research shows that serotonin modulates lateral inhibition among neurons in the striatum by acting on 5-HT1B receptors, while the activation of 5-HT1B receptors does not have a significant impact on the inhibitory effects caused by fast-spiking interneurons.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Vincent Dupuy, Matthieu Prieur, Anne Pizzoccaro, Clara Margarido, Emmanuel Valjent, Joel Bockaert, Tristan Bouschet, Philippe Marin, Severine Chaumont-Dubel
Summary: This study demonstrates the expression and localization of serotonin 5-HT6 receptor (5-HT6R) in the mouse brain at different developmental stages. The receptor is found in various brain regions during early development and is preferentially expressed in specific neuron types and astrocytes in adulthood. The localization of the receptor changes during neonatal stages, suggesting its involvement in neuronal differentiation and psychiatric disorders of neurodevelopmental origin.
NEUROBIOLOGY OF DISEASE
(2023)
Review
Cell Biology
Severine Chaumont-Dubel, Sonya Galant, Matthieu Prieur, Tristan Bouschet, Joel Bockaert, Philippe Marin
Summary: The serotonin (5-HT)(6) receptor is specifically expressed in the central nervous system and plays an important role in neurodevelopment and cognitive processes. Its unique localization in primary cilia of neurons and astrocytes distinguishes it from other serotonin receptors. Pharmacological inhibition of the receptor has been shown to improve cognitive impairment in various models, including neurodevelopmental psychiatric disorders and neurodegenerative diseases.
Article
Biochemistry & Molecular Biology
Kamaludin Dingle, Osama M. Kassem, Fawaz Azizieh, Ghadeer AbdulHussain, Raj Raghupathy
Summary: This study examined the effects of estrogen, progesterone, and dydrogesterone on cytokine profiles in women with recurrent spontaneous miscarriages. The results showed that estrogen had the fewest effects on cytokines, while progesterone and dydrogesterone affected seven out of eight cytokines. The new statistical method identified IFN-gamma, IL-10, and IL-23 as particularly significant for progesterone and dydrogesterone treatments.
Review
Genetics & Heredity
Annie Varrault, Emeric Dubois, Anne Le Digarcher, Tristan Bouschet
Article
Medicine, Research & Experimental
Fawaz Y. Azizieh, Diaa Shehab, Khaled Al Jarallah, Renu Gupta, Raj Raghupathy
BIOMARKER INSIGHTS
(2019)