Article
Clinical Neurology
Giulia Birolini, Gianluca Verlengia, Francesca Talpo, Claudia Maniezzi, Lorena Zentilin, Mauro Giacca, Paola Conforti, Chiara Cordiglieri, Claudio Caccia, Valerio Leoni, Franco Taroni, Gerardo Biella, Michele Simonato, Elena Cattaneo, Marta Valenza
Summary: This study highlights the importance of glial SREBP2 in the pathogenesis of Huntington's disease and demonstrates that AAV-based delivery of SREBP2 to astrocytes can counteract key features of the disease.
Article
Genetics & Heredity
Karolina Pierzynowska, Magdalena Podlacha, Dorota Luszczek, Estera Rintz, Lidia Gaffke, Zuzanna Szczudlo, Marta Tomczyk, Ryszard T. Smolenski, Grzegorz Wegrzyn
Summary: This study identified abnormal hair morphology as a potential simple marker for testing therapeutic effects or disease progression in widely used HD mouse models R6/1 and R6/2.
Article
Biochemistry & Molecular Biology
Roberto Speziale, Camilla Montesano, Giulia Di Pietro, Daniel Oscar Cicero, Vincenzo Summa, Edith Monteagudo, Laura Orsatti
Summary: Huntington's disease (HD) is a genetic condition caused by the expansion of a specific sequence in the huntingtin gene. There is a lack of effective treatments for HD, highlighting the need for reliable mouse models for preclinical studies. This study utilized a urinary liquid chromatography-high-resolution mass spectrometry analysis to identify metabolic changes in different HD mouse models, aiming to improve our understanding of the disease and identify potential biomarkers.
Article
Neurosciences
Mustafa C. Beker, Ahmet B. Caglayan, Serdar Altunay, Elif Ozbay, Nilay Ates, Taha Kelestemur, Berrak Caglayan, Ulkan Kilic, Thorsten R. Doeppner, Dirk M. Hermann, Ertugrul Kilic
Summary: The study revealed the potential role of PDE10A in ischemic stroke, showing that its inhibition with TAK-063 can enhance neurological function, reduce infarct volume, increase neuronal survival, and improve cerebral microcirculation. Furthermore, PDE10A inhibition also reduces the expression of inflammatory cytokines and chemokines.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Neurosciences
Estibaliz Etxeberria-Rekalde, Saioa Alzola-Aldamizetxebarria, Stefanie Flunkert, Isabella Hable, Magdalena Daurer, Joerg Neddens, Birgit Hutter-Paier
Summary: Researchers conducted a comprehensive analysis of R6/2 mice, identifying Ctip2 and TSPO as new markers associated with the motor system and early neuroinflammation, providing a new direction for the study of HD.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Neurosciences
Katerina D. Oikonomou, Elissa J. Donzis, Minh T. N. Bui, Carlos Cepeda, Michael S. Levine
Summary: The study using the R6/2 mouse model found that the amplitude of somatic calcium transients in CPNs of Huntington's disease patients was reduced, but compensated by increased decay times, so that transient areas were similar between genotypes. Ryanodine receptors (RyRs) and L-type calcium channels may be potential targets for therapeutic intervention.
JOURNAL OF NEUROPHYSIOLOGY
(2021)
Article
Biology
Michael T. Maloney, Wei Wang, Sumana Bhowmick, Ivan Millan, Mridu Kapur, Nicolas Herrera, Everett Frost, Elena Y. Zhang, Scott Song, Melissa Wang, Amelia Bora Park, Annabelle Y. Yao, Yanmin Yang
Summary: This article investigates the transport of BDNF in the brain and identifies defects in BDNF transport in Huntington's disease. The study suggests that these transport deficits contribute to the neurodegeneration of striatal neurons. The findings provide insight into potential therapeutic strategies for HD by increasing BDNF levels.
Article
Medicine, Research & Experimental
Keigo Takahashi, Elizabeth M. Eultgen, Sophie H. Wang, Nicholas R. Rensing, Hemanth R. Nelvagal, Joshua T. Dearborn, Olivier Danos, Nicholas Buss, Mark S. Sands, Michael Wong, Jonathan D. Cooper
Summary: This study investigated the nature and progression of neurological and neuropathological changes in Cln2R207X mice, a model for CLN2 disease. It found progressive epileptiform abnormalities and loss of cortical neuron populations, accompanied by microglial activation and astrogliosis. Gene therapy successfully ameliorated the symptoms and prolonged the lifespan of Cln2R207X mice.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Clinical Neurology
Carrie R. Jonak, Manbir S. Sandhu, Samantha A. Assad, Jacqueline A. Barbosa, Mahindra Makhija, Devin K. Binder
Summary: This study demonstrates the beneficial effects of the PDE10A inhibitor TAK-063 on normalizing EEG biomarkers in a mouse model of Fragile X syndrome, suggesting potential for further translational treatment development without noticeable side effects.
Article
Biotechnology & Applied Microbiology
Feng Yue, Changyou Song, Di Huang, Naagarajan Narayanan, Jiamin Qiu, Zhihao Jia, Zhengrong Yuan, Stephanie N. Oprescu, Bruno T. Roseguini, Meng Deng, Shihuan Kuang
Summary: Knockout of the PTEN gene specifically in skeletal muscle can alleviate myofiber degeneration, improve muscle function, reduce inflammation and fibrosis, and enhance the integrity of muscle basement membrane in a DMD animal model.
Article
Biochemistry & Molecular Biology
Luana Tripodi, Davide Molinaro, Francesco Fortunato, Carolina Mella, Barbara Cassani, Yvan Torrente, Andrea Farini
Summary: This study demonstrates that ONX-0914, a selective inhibitor of the PSMB8 subunit of immunoproteasome, improves pathological traits associated with muscle wasting in a mouse model of Duchenne muscular dystrophy. It reduces inflammation, increases regulatory T cells, and buffers oxidative stress, ultimately leading to a decrease in fibrosis. This suggests that ONX-0914 could be a promising therapeutic approach for slowing down muscle mass loss in dystrophic patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Matthias R. Lambert, Janelle M. Spinazzola, Jeffrey J. Widrick, Anna Pakula, James R. Conner, Janice E. Chin, Jane M. Owens, Louis M. Kunkel
Summary: This study identified PDE10A inhibitors that can reduce the manifestation of dystrophic muscle phenotype in zebrafish, suggesting a potential new application for PDE10A inhibitors as a therapeutic for DMD.
Article
Neurosciences
Lu Zhang, Chunqiao Lin, Jiushuang Zhu, Yan He, Meng Zhan, Xiuwen Xia, Ni Yang, Kun Yang, Baojia Wang, Zhanqion Zhong, Yili Wang, Weijun Ding, Youjun Yang
Summary: Maternal immune activation during pregnancy from viral infections is associated with an increased risk of neurodevelopmental disorders in offspring. In this study, we used a mouse model to demonstrate that CBD can alleviate behavioral abnormalities caused by MIA by modulating synaptic transmission. Additionally, we identified the LPI-GPR55 signaling pathway as being involved in CBD's therapeutic effects.
Article
Neurosciences
S. M. Holley, K. D. Oikonomou, C. M. Swift, L. Mohan, B. Matthews, O. Vega, G. Mkrtchyan, C. Cepeda, M. S. Levine
Summary: As Huntington's disease progresses, there is a loss of neurons in the striatum and thinning of the cerebral cortex. This study found reduced connectivity between thalamic cells and their targeted cortical regions in a mouse model of HD, suggesting impaired thalamocortical information transmission.
Article
Multidisciplinary Sciences
Marie Katrin Bondulich, Yilan Fan, Yeojin Song, Flaviano Giorgini, Gillian P. Bates
Summary: KMO depletion in HD mice can normalize dysregulated KP genes in peripheral tissues and increase levels of neuroprotective metabolites, but it does not improve behavioral phenotypes. Peripheral inflammation levels, including pro-inflammatory cytokines, are modulated by KMO deletion, suggesting a potential role in HD pathogenesis.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Feng Yi, Nirvan Rouzbeh, Kasper B. Hansen, Yuelian Xu, Christopher M. Fanger, Earl Gordon, Kathy Paschetto, Frank S. Menniti, Robert A. Volkmann
Article
Cell Biology
Ornella Cuomo, Antonella Casamassa, Paola Brancaccio, Giusy Laudati, Valeria Valsecchi, Serenella Anzilotti, Antonio Vinciguerra, Giuseppe Pignataro, Lucio Annunziato
Article
Cell Biology
G. Pignataro, P. Brancaccio, G. Laudati, V. Valsecchi, S. Anzilotti, A. Casamassa, O. Cuomo, A. Vinciguerra
Article
Radiology, Nuclear Medicine & Medical Imaging
A. R. Coda, S. Anzilotti, F. Boscia, A. Greco, M. Panico, S. Gargiulo, M. Gramanzini, A. Zannetti, S. Albanese, G. Pignataro, L. Annunziato, M. Salvatore, A. Brunetti, P. De Berardinis, Mario Quarantelli, G. Palma, Sabina Pappata
Summary: The study evaluated the feasibility and sensitivity of multimodality PET/CT and MRI imaging for non-invasive characterization of brain microglial/macrophage activation during the acute phase in a mouse model of RR-MS. Results showed significantly increased SUVR and SPIO-Vol values in EAE mice compared with controls in certain brain regions, suggesting the involvement of activated microglia and infiltrated macrophages in disease severity.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2021)
Article
Cell Biology
Emanuela Paldino, Vincenza D'Angelo, Giuseppe Sancesario, Francesca R. Fusco
CELL DEATH DISCOVERY
(2020)
Article
Cell Biology
Emanuela Paldino, Vincenza D'Angelo, Daunia Laurenti, Cecilia Angeloni, Giuseppe Sancesario, Francesca R. Fusco
Article
Neurosciences
Stefano Brunelli, Noemi Gentileschi, Marco Iosa, Francesca Romana Fusco, Valerio Grossi, Silvia Duri, Calogero Foti, Marco Traballesi
RESTORATIVE NEUROLOGY AND NEUROSCIENCE
(2020)
Article
Biochemistry & Molecular Biology
Vincenza D'Angelo, Mauro Giorgi, Emanuela Paldino, Silvia Cardarelli, Francesca R. Fusco, Ilaria Saverioni, Roberto Sorge, Giuseppina Martella, Stefano Biagioni, Nicola B. Mercuri, Antonio Pisani, Giuseppe Sancesario
Summary: The study found regional differences in the expression and aggregation of A2A receptors in the basal ganglia of a DYT1 mouse model of dystonia, with varying levels of expression observed in different subpopulations of neurons. Based on the different expression patterns of A2A receptors among neuronal subpopulations, it suggests that the pathophysiology of dystonia may be associated with a functional imbalance between the indirect and direct pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Natascia Guida, Luigi Mascolo, Angelo Serani, Ornella Cuomo, Serenella Anzilotti, Paola Brancaccio, Giuseppe Pignataro, Pasquale Molinaro, Lucio Annunziato, Luigi Formisano
Summary: The study revealed that the GATA3/KMT2A complex epigenetically activates NCX3 gene transcription during ischemic preconditioning, playing a crucial role in neuroprotection.
Review
Biochemistry & Molecular Biology
Emanuela Paldino, Francesca Romana Fusco
Summary: Huntington's disease is a neurodegenerative disease caused by a mutation in the IT15 gene encoding huntingtin protein. Inflammation plays a significant role in neuronal death, making drugs targeting inflammation powerful tools for treating Huntington's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Emanuela Paldino, Vincenza D'angelo, Mariangela Massaro Cenere, Ezia Guatteo, Simone Barattucci, Giorgia Migliorato, Nicola Berretta, Olaf Riess, Giuseppe Sancesario, Nicola Biagio Mercuri, Francesca Romana Fusco
Summary: This study used immunohistochemical studies to investigate neuropathological changes in a rat transgenic model of Parkinson's disease (PD). It found that in the advanced stages of the disease, there was neuronal loss in the dorsolateral part of the striatum, along with a dramatic loss of parvalbumin interneurons. A marked decrease in the neurotrophic factor called glial-derived neurotrophic factor (GDNF) was also observed in the striatum and substantia nigra of these animals. This confirms the involvement of the striatum in PD pathophysiology and the importance of GDNF in maintaining the health of the substantia nigra.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Ada Ledonne, Mariangela Massaro Cenere, Emanuela Paldino, Vincenza D'Angelo, Sebastian Luca D'Addario, Nicolas Casadei, Annalisa Nobili, Nicola Berretta, Francesca R. Fusco, Rossella Ventura, Giuseppe Sancesario, Ezia Guatteo, Nicola Biagio Mercuri
Summary: Prolonged overexpression of alpha-synuclein has detrimental effects on the structural and functional properties of substantia nigra pars compacta dopamine neurons, including compromised soma and dendritic arborization, increased firing activity, and altered ion channel function.
MOVEMENT DISORDERS
(2023)
Review
Neurosciences
Jesse E. Hanson, Hongjie Yuan, Riley E. Perszyk, Tue G. Banke, Hao Xing, Ming-Chi Tsai, Frank S. Menniti, Stephen F. Traynelis
Summary: N-methyl-D-aspartate (NMDA) receptors play a role in excitatory synaptic transmission, are present throughout the central nervous system, and are involved in synaptic plasticity. NMDA receptor modulators have shown potential in treating psychiatric disorders, neurodevelopmental disorders, and neurodegenerative conditions. Recent research has discovered that certain NMDA receptor inhibitors can rapidly and significantly alleviate depression by inducing long-lasting changes in the brain. This has led to new studies exploring the therapeutic applications of NMDA receptor antagonists. Positive allosteric modulators of NMDA receptors are also being investigated for enhancing synaptic function in diseases with NMDA receptor dysfunction. However, the use of NMDA receptor modulators comes with potential risks. Therefore, further research is needed to fully understand and harness the therapeutic potential of targeting this important receptor class.
NEUROPSYCHOPHARMACOLOGY
(2023)
Meeting Abstract
Clinical Neurology
Giuseppe Sancesario, Vincenza D'Angelo, Giorgio Bernardi, Francesca Fusco, Giuseppina Martella, Emanuela Paldino, Silvia Cardarelli, Mauro Giorgi, Nicola Mercuri, Antonio Pisani
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2021)
Article
Medicine, Research & Experimental
Antonio Vinciguerra, Pasquale Cepparulo, Serenella Anzilotti, Ornella Cuomo, Valeria Valsecchi, Salvatore Amoroso, Lucio Annunziato, Giuseppe Pignataro