Article
Multidisciplinary Sciences
Wan Yun Ho, Li-Ling Chak, Jin-Hui Hor, Fujia Liu, Sandra Diaz-Garcia, Jer-Cherng Chang, Emma Sanford, Maria J. Rodriguez, Durgadevi Alagappan, Su Min Lim, Yik-Lam Cho, Yuji Shimizu, Alfred Xuyang Sun, Sheue-Houy Tyan, Edward Koo, Seung Hyun Kim, John Ravits, Shi-Yan Ng, Katsutomo Okamura, Shuo-Chien Ling
Summary: In this study, researchers analyzed the miRNA repertoires in spinal cords and hippocampi from ALS-FUS mice to understand the role of FUS-dependent miRNA deregulation in ALS. They identified differentially expressed miRNAs between CNS regions and disease states. One up-regulated miRNA, miR-1197, was found to target the pro-survival pseudokinase Trib2. They also observed reduced TRIB2 expression in motor neurons derived from ALS patients. Stabilizing TRIB2 protein with a cancer drug improved the survival of human motor neurons, including those from a sporadic ALS patient. These findings suggest that profiling miRNAs can help uncover the molecular mechanisms underlying selective vulnerability in ALS, and TRIB2 may be a potential therapeutic target.
Review
Biochemistry & Molecular Biology
Sophie Layalle, Laetitia They, Sarah Ourghani, Cedric Raoul, Laurent Soustelle
Summary: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the degeneration of motoneurons. Fruit flies have emerged as a versatile model for studying ALS, providing insights into cellular mechanisms and potential therapeutic targets for future treatments. Research on fruit fly ALS models has revealed novel pathogenic mechanisms and identified disease-modifying genes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Simona Rossi, Mauro Cozzolino
Summary: Amyotrophic Lateral Sclerosis is a neurological disease primarily affecting motor neurons, with neuroinflammatory processes playing a significant role in its pathogenesis. The dysregulation of RNA metabolism and its association with neuroinflammation in ALS remains poorly defined.
Article
Biochemistry & Molecular Biology
Giada Zanini, Valentina Selleri, Milena Nasi, Anna De Gaetano, Ilaria Martinelli, Giulia Gianferrari, Francesco Demetrio Lofaro, Federica Boraldi, Jessica Mandrioli, Marcello Pinti
Summary: This study reports the clinical and biological features of an ALS patient with pA382T mutation in TPD-43 protein. The mutation leads to significant alterations in neuronal proteome, particularly impacting mitochondrial metabolic pathways and the endoplasmic reticulum. The findings suggest that mitochondrial dysfunction and misplacement of mitochondrial DNA may be mechanisms contributing to ALS caused by this mutation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Sonu Sahadevan, Katharina M. Hembach, Elena Tantardini, Manuela Perez-Berlanga, Marian Hruska-Plochan, Salim Megat, Julien Weber, Petra Schwarz, Luc Dupuis, Mark D. Robinson, Pierre De Rossi, Magdalini Polymenidou
Summary: Mutations in the RNA-binding protein FUS disrupt its nuclear localization and contribute to amyotrophic lateral sclerosis. Accumulation of synaptic FUS in early disease leads to synaptic impairment, potentially representing an initial trigger of neurodegeneration. The study identifies proteins associated with synapse organization and plasticity that are differentially regulated in an ALS mouse model.
NATURE COMMUNICATIONS
(2021)
Article
Clinical Neurology
Hadjara Sidibe, Yousra Khalfallah, Shangxi Xiao, Nicolas B. Gomez, Hana Fakim, Elizabeth M. H. Tank, Genevieve Di Tomasso, Eric Bareke, Anais Aulas, Paul M. McKeever, Ze'ev Melamed, Laurie Destroimaisons, Jade-Emmanuelle Deshaies, Lorne Zinman, J. Alex Parker, Pascale Legault, Martine Tetreault, Sami J. Barmada, Janice Robertson, Christine Vande Velde
Summary: The study reveals that TDP-43 stabilizes G3BP1 transcripts, nuclear TDP-43 depletion is sufficient to reduce G3BP1 protein levels, and G3BP1 transcripts are reduced in neurons of ALS/FTD patients with TDP-43 cytoplasmic inclusions/nuclear depletion. These findings suggest that loss of function of TDP-43 and G3BP1 may contribute to ALS/FTD pathogenesis.
Article
Biochemistry & Molecular Biology
Greta Grassmann, Mattia Miotto, Lorenzo Di Rienzo, Federico Salaris, Beatrice Silvestri, Elsa Zacco, Alessandro Rosa, Gian Gaetano Tartaglia, Giancarlo Ruocco, Edoardo Milanetti
Summary: This article investigates the protein aggregation process in ALS, providing a computational model of interaction based on the evaluation of shape complementarity at the molecular interfaces. The study proposes and assesses possible association mechanisms between CTFs, and performs molecular docking and additional MD simulations to propose possible complexes and evaluate their stability, focusing on high shape complementarity and involvement of beta 3 and beta 5 strands at the interfaces.
Article
Biochemistry & Molecular Biology
Akira Ishiguro, Akira Katayama, Akira Ishihama
Summary: The study found that TDP-43 and FUS have different target selectivity in binding to G4-RNA, with TDP-43 recognizing parallel-stranded G4-DNA/RNAs and FUS binding to all three types of G4-DNA/RNAs.
Article
Multidisciplinary Sciences
Emilie Bertrand, Clement Demongin, Ioana Dobra, Juan Carlos Rengifo-Gonzalez, Anastasia S. Singatulina, Maria V. Sukhanova, Olga I. Lavrik, David Pastre, Loic Hamon
Summary: FUS is an RNA-binding protein that can assemble into nanofibrils and form insoluble fibrillar aggregates. This process is inhibited by binding to mRNA or phosphorylation of its prion-like domain. The formation of these nanofibrils may serve as seeds for the development of pathological inclusions.
SCIENTIFIC REPORTS
(2023)
Article
Clinical Neurology
Yuting Ren, Siyuan Li, Siyu Chen, Xiaosun Sun, Fei Yang, Hongfen Wang, Mao Li, Fang Cui, Xusheng Huang
Summary: The levels of plasma TDP-43 and pTDP-43 were significantly higher in ALS patients compared to healthy controls, with plasma TDP-43 showing high sensitivity and specificity in differentiating between the two groups and indicating disease progression.
FRONTIERS IN NEUROLOGY
(2021)
Article
Multidisciplinary Sciences
Jelena Scekic-Zahirovic, Inmaculada Sanjuan-Ruiz, Vanessa Kan, Salim Megat, Pierre De Rossi, Stephane Dieterle, Raphaelle Cassel, Marguerite Jamet, Pascal Kessler, Diana Wiesner, Laura Tzeplaeff, Valerie Demais, Sonu Sahadevan, Katharina M. Hembach, Hans-Peter Muller, Gina Picchiarelli, Nibha Mishra, Stefano Antonucci, Sylvie Dirrig-Grosch, Jan Kassubek, Volker Rasche, Albert Ludolph, Anne-Laurence Boutillier, Francesco Roselli, Magdalini Polymenidou, Clotilde Lagier-Tourenne, Sabine Liebscher, Luc Dupuis
Summary: Mutations in the RNA binding protein FUS are associated with ALS. Here the authors show that in FUS knock-in mice there is a progressive increase in neuronal activity in the frontal cortex which is associated with altered synaptic gene expression.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Leanne Jiang, Shyuan T. Ngo
Summary: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disorder with no cure available. TDP-43, a protein found in more than 97% of ALS patients, is believed to play a crucial role in the disease process. Targeting TDP-43 could be a promising approach for future therapeutic investigations.
Article
Biochemistry & Molecular Biology
Zachary R. Grese, Alliny C. S. Bastos, Lohany D. Mamede, Rachel L. French, Timothy M. Miller, Yuna M. Ayala
Summary: TDP-43 is an RNA-binding protein that forms ribonucleoprotein condensates through liquid-liquid phase separation, playing a central role in regulating gene expression and protein homeostasis. RNA binding promotes TDP-43 condensation through specific interactions, maintaining the liquid-like properties of condensates. Defects in this RNA-mediated activity may contribute to TDP-43-associated pathogenesis, particularly in neurodegenerative disorders such as ALS and frontotemporal dementia.
Article
Geriatrics & Gerontology
Zhe Long, Muireann Irish, John R. Hodges, Glenda Halliday, Olivier Piguet, James R. Burrell
Summary: Clinical and pathological heterogeneity is common in patients with frontotemporal lobar degeneration (FTLD) pathology. Characteristics that differentiate between FTLD-TDP and FTLD-tau, as well as different subtypes within FTLD-TDP, were investigated. Amyotrophic lateral sclerosis features were highly specific for FTLD-TDP, which showed greater atrophy than FTLD-tau. TDP-43 subtyping may have more clinical utility in distinguishing different profiles within FTLD-TDP.
NEUROBIOLOGY OF AGING
(2021)
Review
Biochemistry & Molecular Biology
Alistair Wood, Yuval Gurfinkel, Nicole Polain, Wesley Lamont, Sarah Lyn Rea
Summary: ALS and FTLD are neurodegenerative disorders with pathological, clinical, and genetic overlaps. The primary pathological protein, TDP-43, is observed in aggregates in affected tissues in majority of cases. Disease pathogenesis involves changes in RNA splicing, abnormal stress granules, mitochondrial dysfunction, and other cellular processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Clinical Neurology
Michael J. Strong, Julianne Santarosa, Timothy P. Sullivan, Noojan Kazemi, Jacob R. Joseph, Osama N. Kashlan, Mark E. Oppenlander, Nicholas J. Szerlip, Paul Park, Clay M. Elswick
Summary: This review assesses and describes thoracic spine localization techniques. The study found that while there are multiple methods available for accurately localizing lesions in the thoracic spine, each method has its own advantages and disadvantages. The choice of localization technique ultimately depends on the specific patient and the preference of the spine surgeon.
JOURNAL OF NEUROSURGERY-SPINE
(2022)
Editorial Material
Clinical Neurology
Michael J. Strong, Sravanthi Koduri, Whitney E. Muhlestein, Yamaan S. Saadeh, Paul Park
OPERATIVE NEUROSURGERY
(2022)
Article
Clinical Neurology
Whitney E. Muhlestein, Michael J. Strong, Timothy J. Yee, Yamaan S. Saadeh, Paul Park
OPERATIVE NEUROSURGERY
(2022)
Editorial Material
Clinical Neurology
Moustafa Hadi, Yamaan S. Saadeh, Michael J. Strong, Zoey Chopra, Osama N. Kashlan, Paul Park
OPERATIVE NEUROSURGERY
(2022)
Editorial Material
Clinical Neurology
Yamaan S. Saadeh, Michael J. Strong, Whitney E. Muhlestein, Sravanthi Koduri, Paul Park
OPERATIVE NEUROSURGERY
(2022)
Editorial Material
Clinical Neurology
Whitney E. Muhlestein, Yamaan S. Saadeh, Michael J. Strong, Sravanthi Koduri, Timothy J. Yee, Paul Park
OPERATIVE NEUROSURGERY
(2022)
Review
Oncology
Michael J. Strong, Sravanthi Koduri, Jodi A. Allison, Cecilia M. Pesavento, Sebele Ogunsola, Oludotun Ogunsola, Timothy J. Yee, Siri Sahib S. Khalsa, Yamaan S. Saadeh, Jacob R. Joseph, Osama N. Kashlan, Paul Park, Mark E. Oppenlander, Nicholas J. Szerlip
Summary: This article provides a systematic literature review on osseous metastases of GBM, highlighting the high incidence of metastasis to the vertebral column. The authors suggest that workup for metastatic disease, especially involving the spinal column, should be considered in symptomatic patients. They also propose a management algorithm for GBM vertebral column metastases based on the International Spine Oncology Consortium guidelines.
JOURNAL OF NEURO-ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Aqila A. Ahmed, Michael J. Strong, Xiaofeng Zhou, Tyler Robinson, Sabrina Rocco, Geoffrey W. Siegel, Gregory A. Clines, Bethany B. Moore, Evan T. Keller, Nicholas J. Szerlip
Summary: Approximately 400,000 people in the U.S. have bone metastases, mostly occurring in the spine. The preference for cancer to metastasize to the bone is seen across various types of cancer, with prostate, breast, and lung cancer having the highest incidence. Immune cells play a significant role in tumor growth and progression in bone disease, and studying the immune landscape differences between axial and appendicular bones in a noncancerous setting could provide insights into the distribution and growth of bone metastases.
Article
Clinical Neurology
Dimitri Benner, Benjamin K. Hendricks, Cyrus Elahi, Michael D. White, Gary Kocharian, Leonardo E. Albertini Sanchez, Kyle E. Zappi, Andrew L. A. Garton, Joseph A. Carnevale, Theodore H. Schwartz, Ehsan Dowlati, Daniel R. Felbaum, Kenneth D. Sack, Walter C. Jean, Andrew K. Chan, John F. Burke, Praveen Mummaneni, Michael J. Strong, Timothy J. Yee, Mark E. Oppenlander, Mariam Ishaque, Mark E. Shaffrey, Hasan R. Syed, Michael T. Lawton
Summary: During the COVID-19 surge, operative volume in neurosurgery decreased significantly by 58.5% compared to the previous year. The infection rates within the departments' counties were associated with decreased operative volume and increased patient acuity. Different subspecialties experienced distinct changes in surgical volume and proportions.
WORLD NEUROSURGERY
(2022)
Review
Clinical Neurology
Michael J. J. Strong, Michael Swash
Summary: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two seemingly disparate syndromes, but they share common molecular vulnerabilities. The relationship between ALS and FTD is not based on unique neuroanatomic correlations, but rather on shared underlying mechanisms.
Editorial Material
Clinical Neurology
Hunter R. Kiesling, Michael J. Strong, Yamaan S. Saadeh, Paul Park
OPERATIVE NEUROSURGERY
(2022)
Review
Biochemistry & Molecular Biology
Michael J. Strong
Summary: As the world continues to battle the COVID-19 pandemic, there is growing evidence suggesting that the long-term neurological sequelae of the viral infection will be significant and enduring. This pandemic is unique due to its impact on an aging population, putting survivors at increased risk of developing neurodegenerative conditions. The SARS-CoV-2 virus itself, as well as its key proteins, have been implicated in potential neurodegenerative processes.
JOURNAL OF NEUROCHEMISTRY
(2023)
Meeting Abstract
Oncology
Michael Strong, Varun Kathawate, Peyton Goethe, Lila Tudrick, Joseph Linzey, Ayobami Ward, Mark Zaki, Rushikesh Joshi, William Jackson, Nicholas Szerlip
Review
Clinical Neurology
Sravanthi Koduri, Michael J. Strong, Yamaan S. Saadeh, Whitney E. Muhlestein, Paul Park
OPERATIVE NEUROSURGERY
(2022)
Article
Clinical Neurology
Ibrahim Youssef, Yamaan S. Saadeh, Michael J. Strong, Paul Park
OPERATIVE NEUROSURGERY
(2022)
