Article
Neurosciences
Dylan V. Neel, Himanish Basu, Georgia Gunner, Matthew D. Bergstresser, Richard M. Giadone, Haeji Chung, Rui Miao, Vicky Chou, Eliza Brody, Xin Jiang, Edward Lee, Michelle E. Watts, Christine Marques, Aaron Held, Brian Wainger, Clotilde Lagier-Tourenne, Yong-Jie Zhang, Leonard Petrucelli, Tracy L. Young-Pearse, Alice S. Chen-Plotkin, Lee L. Rubin, Judy Lieberman, Isaac M. Chiu
Summary: Mitochondrial dysfunction and axon loss are key features of neurologic diseases, and Gasdermin (GSDM) proteins, including GSDME, play a role in these processes. Proteins associated with FTD/ALS, such as TDP-43 and PR-50, induce GSDME-mediated damage to mitochondria and neurite loss. Knockdown of GSDME protects against neurite loss in ALS patient iPSC-derived motor neurons, and knockout of GSDME in SOD1G93A ALS mice improves survival, motor function, and reduces neuroinflammation, highlighting the importance of GSDME in neuro-degeneration.
Article
Biochemistry & Molecular Biology
Wei-Fang Chang, Min Peng, Jing Hsu, Jie Xu, Huan-Chieh Cho, Hsiu-Mei Hsieh-Li, Ji-Long Liu, Chung-Hao Lu, Li-Ying Sung
Summary: SMN is crucial for RNA spliceosome assembly and plays important roles in stem cell biology. Overexpression of SMN enhances the proliferation and potency of SSCs, positively influencing spermatogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Stefano Zoccolella, Alessandro Introna, Giammarco Milella, Antonella Mastronardi, Giovanni Iliceto, Eustachio D'Errico, Angela Fraddosio, Isabella Laura Simone
Summary: This study aimed to evaluate a cohort of LMNP patients and found that TMS abnormalities did not impact survival time but accelerated disease progression, leading to a faster progression to King's 4 stage.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2021)
Article
Cell Biology
Angela Koh, Menachem Viktor Sarusie, Jurgen Ohmer, Utz Fischer, Christoph Winkler, Thorsten Wohland
Summary: The research found that a decrease in SMN protein levels in patients with Spinal Muscular Atrophy may lead to transcript splicing defects, rather than active transport in axons; SMN acts as a chaperone for the assembly of snRNP and mRNP complexes in motor neurons, playing an important role.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Irene Faravelli, Giulietta M. Riboldi, Paola Rinchetti, Francesco Lotti
Summary: RNA exists and functions with RNA binding proteins (RBPs) in a cell to regulate the RNA life cycle. Molecular chaperones play a central role in this regulation by ensuring correct interactions and aiding the biogenesis of large RNA-protein complexes. Impairment of accurate formation of these complexes can lead to disease. The survival motor neuron (SMN) protein is an example of this, with deficiency causing spinal muscular atrophy (SMA). Understanding the role of SMN in gene expression and disruption of SMN-dependent RNA pathways is important for understanding SMA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Rachel James, Helena Chaytow, Leire M. Ledahawsky, Thomas H. Gillingwater
Summary: SMA is an autosomal recessive motor neuron disease caused by mutations in the SMN1 gene. The development of combinatorial therapies for SMA is necessary, with mitochondria being a relevant target for such therapies. Understanding mitochondrial dysfunction in SMA may lead to the development of targeted mitochondrial therapies with potential benefits for other motor neuron diseases and neurodegenerative disorders.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jyotishman Veepaschit, Aravindan Viswanathan, Remy Bordonne, Clemens Grimm, Utz Fischer
Summary: The study identified and structurally determined the SMN complex from the lower eukaryote Schizosaccharomyces pombe, revealing that the core of the complex is formed by multiple copies of SMN tethered through its C-terminal alpha-helices, creating a central platform onto which Gemin8 binds and recruits Gemins 6 and 7, with Sm proteins located on the periphery waiting to join with UsnRNA.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Mar Costa-Roger, Laura Blasco-Perez, Ivon Cusco, Eduardo F. Tizzano
Summary: Comprehensive study of the SMN1 and SMN2 genes is crucial for better prediction of SMA in positive neonatal screening cases and early diagnosis to start treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Judyta K. Juranek, Konark Mukherjee, Reinhard Jahn, Jia-Yi Li
Summary: Synaptic transmission relies on neurotransmitters stored in synaptic vesicles and released at the active zone. Research shows a robust bi-directional, coordinated trafficking of synaptic vesicle and active zone proteins in peripheral nerves, which plays a critical role in neuronal function and neurodegenerative diseases.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Giulietta M. Riboldi, Irene Faravelli, Takaaki Kuwajima, Nicolas Delestree, Georgia Dermentzaki, Mariangels De Planell-Saguer, Paola Rinchetti, Le Thi Hao, Christine C. Beattie, Stefania Corti, Serge Przedborski, George Z. Mentis, Francesco Lotti
Summary: Sumoylation is crucial for the assembly and function of the SMN complex, and its loss impairs SMN's ability to correct specific deficits in the sensory-motor circuit of animal models of spinal muscular atrophy.
NATURE COMMUNICATIONS
(2021)
Article
Clinical Neurology
Chaoping Hu, Xihua Li, Yiyun Shi, Xiaomei Zhu, Lei Zhao, Wenhui Li, Shuizhen Zhou, Yi Wang
Summary: This study provides insight into the comprehensive management and profile of different types of SMA patients in China, highlighting the importance of higher SMN2 copies for better survival and ambulation preservation. Patients receiving regular rehabilitation may have better joint function preservation.
FRONTIERS IN NEUROLOGY
(2022)
Article
Neurosciences
Jeong-Ki Kim, Narendra N. Jha, Tomoyuki Awano, Charlotte Caine, Kishore Gollapalli, Emily Welby, Seung-Soo Kim, Andrea Fuentes-Moliz, Xueyong Wang, Zhihua Feng, Fusako Sera, Taishi Takeda, Shunichi Homma, Chien -Ping Ko, Lucia Tabares, Allison D. Ebert, Mark M. Rich, Umrao R. Monani
Summary: Scientists have discovered a synaptic chaperone variant called Hspa8G470R that can suppress spinal muscular atrophy (SMA) and improve neuromuscular function in model mice. The variant alters SMN2 splicing and stimulates the formation of a tripartite chaperone complex critical for synaptic homeostasis. This study provides new insights into how deficiency of the SMN protein causes motor neuron disease.
Article
Clinical Neurology
Danielle Leighton, Morad Ansari, Judith Newton, David Parry, Elaine Cleary, Shuna Colville, Laura Stephenson, Juan Larraz, Micheala Johnson, Emily Beswick, Michael Wong, Jenna Gregory, Javier Carod Artal, Richard Davenport, Callum Duncan, Ian Morrison, Colin Smith, Robert Swingler, Ian Deary, Mary Porteous, Timothy Aitman, Siddharthan Chandran, George Gorrie, Suvankar Pal, Carolyn Lothian Birth Cohorts Grp, CARE-MND Consortium
Summary: This study investigated the phenotypes and genotypes of a cohort of long-surviving individuals with motor neuron disease (MND). The findings suggest that long survivors are characterized by younger age at onset, increased prevalence of primary lateral sclerosis (PLS), and longer diagnostic delay. Genetic analysis revealed potentially pathogenic variants in several MND-associated genes.
JOURNAL OF NEUROLOGY
(2023)
Article
Multidisciplinary Sciences
Edgar Buhl, Benjamin Kottler, James J. L. Hodge, Frank Hirth
Summary: In insects, thermoreceptors and neurons play critical roles in mediating temperature sensation and thermoresponsive motor behavior. Experimental findings in Drosophila indicate that different functions of ellipsoid body ring neurons R1-R4 are involved in integrating thermosensory information and regulating adaptive motor responses to changes in external temperature. Further research on the neural mechanisms underlying sensory-motor transformation of temperature changes in fruit flies sheds light on the complexity of thermoregulation in ectothermal animals.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Emily J. Reedich, Martin Kalski, Nicholas Armijo, Gregory A. Cox, Christine J. DiDonato
Summary: Spinal muscular atrophy (SMA) is a neuromuscular disease caused by genetic deficiency of the SMN protein. Studies have shown activation of the p53 and p21 pathways in SMA mice, but they are not primary drivers of motor neuron death in milder SMA mouse models like Smn(2B/-).
EXPERIMENTAL NEUROLOGY
(2021)
Article
Virology
Leny Jose, Elliot J. Androphy, Marsha DeSmet
JOURNAL OF VIROLOGY
(2020)
Article
Virology
Timra Gilson, Sara Culleton, Fang Xie, Marsha DeSmet, Elliot J. Androphy
JOURNAL OF VIROLOGY
(2020)
Article
Virology
Leny Jose, Marsha DeSmet, Elliot J. Androphy
JOURNAL OF VIROLOGY
(2020)
Article
Biology
Anne Rietz, Kevin J. Hodgetts, Hrvoje Lusic, Kevin M. Quist, Erkan Y. Osman, Christian L. Lorson, Elliot J. Androphy
Summary: Researchers established a tunable model of mild and moderate SMA using a splicing compound, demonstrating prevention of severe SMA phenotype and phenotypic recovery when administered on day eight.
LIFE SCIENCE ALLIANCE
(2021)
Article
Cell & Tissue Engineering
Kristina Dobrindt, Daisy A. Hoagland, Carina Seah, Bibi Kassim, Callan P. O'Shea, Aleta Murphy, Marina Iskhakova, Michael B. Fernando, Samuel K. Powell, P. J. Michael Deans, Ben Javidfar, Cyril Peter, Rasmus Moller, Skyler A. Uhl, Meilin Fernandez Garcia, Masaki Kimura, Kentaro Iwasawa, John F. Crary, Darrell N. Kotton, Takanori Takebe, Laura M. Huckins, Benjamin R. tenOever, Schahram Akbarian, Kristen J. Brennand
Summary: The host response to SARS-CoV-2 shows significant variability among individuals, with genetic variants also influencing susceptibility to infection. Research suggests that common genetic variations, such as the single-nucleotide polymorphism (rs4702), can impact viral infection.
Article
Genetics & Heredity
John F. Fullard, Hao-Chih Lee, Georgios Voloudakis, Shengbao Suo, Behnam Javidfar, Zhiping Shao, Cyril Peter, Wen Zhang, Shan Jiang, Andre Corvelo, Heather Wargnier, Emma Woodoff-Leith, Dushyant P. Purohit, Sadhna Ahuja, Nadejda M. Tsankova, Nathalie Jette, Gabriel E. Hoffman, Schahram Akbarian, Mary Fowkes, John F. Crary, Guo-Cheng Yuan, Panos Roussos
Summary: Despite the absence of detectable SARS-CoV-2 in the brain at the time of death, the findings suggest significant and persistent neuroinflammation in patients with acute COVID-19. Single-cell transcriptomics studies revealed transcriptional changes in various cell types in specific brain regions of COVID-19 patients, including cellular activation, mobility, and phagocytosis.
Review
Microbiology
Leny Jose, Timra Gilson, Elliot J. Androphy, Marsha DeSmet
Summary: HPV is a DNA tumor virus that causes various cancers, with the E2 protein being essential for viral replication and regulated by various modifications. Recent advancements have identified post translational modifications within E2 that control viral replication.
Article
Multidisciplinary Sciences
Sandhya Chandrasekaran, Sergio Espeso-Gil, Yong-Hwee Eddie Loh, Behnam Javidfar, Bibi Kassim, Yueyan Zhu, Yuan Zhang, Yuhao Dong, Lucy K. Bicks, Haixin Li, Prashanth Rajarajan, Cyril J. Peter, Daijing Sun, Esperanza Agullo-Pascual, Marina Iskhakova, Molly Estill, Bluma J. Lesch, Li Shen, Yan Jiang, Schahram Akbarian
Summary: The study reveals the role of upregulation of endogenous retroviral sequences in brain structure, with a specific focus on ERV2 sequences in neuron-specific chromatin domains in the cerebral cortex of adult mice. Comparative analysis between wild-derived and laboratory inbred mice further demonstrates the impact of recent ERV2 expansions on neuronal reconfigurations and chromosomal contact frequencies in the murine germline, highlighting the importance of neuronal chromosomal organization in transcriptional regulation and neuronal tropism.
NATURE COMMUNICATIONS
(2021)
Article
Neurosciences
Feilin Liu, Dmytro Morderer, Melissa C. Wren, Sara A. Vettleson-Trutza, Yanzhe Wang, Benjamin E. Rabichow, Michelle R. Salemi, Brett S. Phinney, Bjorn Oskarsson, Dennis W. Dickson, Wilfried Rossoll
Summary: The most common inherited cause of ALS and FTD is the expansion of GGGGCC repeats in the C9orf72 gene. In addition to haploinsufficiency and toxic RNA foci, other disease mechanisms are involved. Through the use of the BioID approach, it was found that DPR aggregates are associated with specific proteins that play important roles in protein folding and degradation. Heat shock proteins and co-chaperones were found to be closely associated with one of the DPRs, poly-GA, and may play a significant role in reducing its aggregation.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Editorial Material
Neurosciences
Wilfried Rossoll, Ravindra N. Singh
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Virology
Leny Jose, Elliot J. Androphy, Marsha DeSmet
Summary: This study demonstrates that methylation of Brd4 by SETD6 in HPV-episomal cells is necessary for the activation of viral transcription. It reveals a novel regulatory mechanism involving E2, Brd4, and SETD6 in the HPV life cycle, shedding light on the multiple roles of Brd4 in viral pathogenesis.
JOURNAL OF VIROLOGY
(2022)
Article
Neurosciences
Bilal Khalil, Deepak Chhangani, Melissa C. Wren, Courtney L. Smith, Jannifer H. Lee, Xingli Li, Christian Puttinger, Chih-Wei Tsai, Gael Fortin, Dmytro Morderer, Junli Gao, Feilin Liu, Chun Kim Lim, Jingjiao Chen, Ching-Chieh Chou, Cara L. Croft, Amanda M. Gleixner, Christopher J. Donnelly, Todd E. Golde, Leonard Petrucelli, Bjorn Oskarsson, Dennis W. Dickson, Ke Zhang, James Shorter, Shige H. Yoshimura, Sami J. Barmada, Diego E. Rincon-Limas, Wilfried Rossoll
Summary: The study found that members of the nuclear import receptor protein family can reduce the formation of pathological TDP-43 aggregates. Using KPNB1 as a model, it was discovered that its activity depends on the prion-like C-terminal region of TDP-43, mediating co-aggregation with nucleoporins such as Nup62. KPNB1 acts as a molecular chaperone in these co-aggregates, reversing the aberrant phase transition of Nup62 and TDP-43.
MOLECULAR NEURODEGENERATION
(2022)
Article
Microbiology
Sriramana Kanginakudru, Timra Gilson, Leny Jose, Elliot J. Androphy
Summary: Epidemiological studies have shown that caffeinated coffee can reduce the risk of oropharyngeal cancer caused by HPV. Caffeine inhibits the DNA damage response pathway, which affects the replication of HPV. Caffeine reduces the HPV copy number in the early stage of infection but increases the copy number of HPV episomes in later stages.
Article
Neurosciences
Talanjeri Gopalakrishna Sahana, Katherine Johnson Chase, Feilin Liu, Thomas E. Lloyd, Wilfried Rossoll, Ke Zhang
Summary: Stress granules, RNA/protein condensates formed in cells under stress, are closely related to the pathogenesis of ALS and FTD. The most common genetic cause of these diseases is the mutation in the C9orf72 gene, which leads to the formation of toxic dipeptide repeats. In this study, it was found that the two most toxic dipeptide repeats, poly(GR) and poly(PR), activate the JNK pathway via the ER stress response protein IRE1, promoting stress granule assembly by inducing histone 3 phosphorylation and thus contributing to the neurodegeneration seen in C9ALS/FTD.
JOURNAL OF NEUROSCIENCE
(2023)
Editorial Material
Neurosciences
Feilin Liu, Wilfried Rossoll
Summary: In this study, Liu et al. identified DAXX as a protein that binds to the C9orf72 hexanucleotide repeat expansion DNA. They found that DAXX plays a role in initiating epigenetic modifications and chromatin remodeling, leading to C9orf72 haploinsufficiency, inhibiting its stress-inducible expression, and mediating both loss and toxic gain-of-function pathology.