Article
Multidisciplinary Sciences
Sara Cazzaro, Jung-A A. Woo, Xinming Wang, Tian Liu, Shanon Rego, Teresa R. Kee, Yeojung Koh, Edwin Vazquez-Rosa, Andrew A. Pieper, David E. Kang
Summary: Oxidative damage is an early driver of pathology in Alzheimer's disease and related dementias. The Slingshot homolog-1 (SSH1) acts as a counterweight to neuroprotective Nrf2 and drives oxidative damage by suppressing Nrf2 signaling and enhancing Keap1-Nrf2 interaction. Inhibiting SSH1-mediated Nrf2 suppression may provide new neuroprotective therapies for AD and related dementias.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Isidro Ferrer, Pol Andres-Benito, Karina Ausin, Paz Cartas-Cejudo, Mercedes Lachen-Montes, Jose Antonio del Rio, Joaquin Fernandez-Irigoyen, Enrique Santamaria
Summary: The over-expression of human tau without pre-tangle and neurofibrillary tangle formation leads to an imbalance in the phosphorylation profile of specific proteins, particularly those involved in the cytoskeletal-membrane-signaling axis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Neurosciences
Kristian F. Odfalk, Kevin F. Bieniek, Sarah C. Hopp
Summary: This article reviews the intersection between microglia and tau from the perspectives of neuropathology, neuroimaging, genetics, transcriptomics, and molecular biology. Microglia play both positive and negative roles in regulating tau pathology, with the ability to mitigate tau spread by degrading internalized tau seeds, but detrimental consequences occur when these seeds cannot be degraded.
PROGRESS IN NEUROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Dhwani S. Korde, Christian Humpel
Summary: This study investigates the spreading of P301S aggregated tau in the brain using organotypic slice cultures and collagen hydrogels as a protein delivery system. The results show that P301S aggregated tau spreads to different areas of the brain in a time-dependent manner, and this spreading is interrupted when the neuroanatomical pathways are lesioned. The study provides a novel experimental approach to investigate tau pathology.
Review
Immunology
Nastaran Karimi, Feyza Bayram Catak, Ebru Arslan, Amene Saghazadeh, Nima Rezaei
Summary: Tau, a protein associated with more than 25 neurological disorders, has been the target of research for finding novel therapeutic agents. This article reviews the latest animal and clinical studies on tau-based immunotherapies and drugs for Alzheimer's disease and progressive supranuclear palsy.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Review
Clinical Neurology
Sarah Houben, Megane Homa, Zehra Yilmaz, Karelle Leroy, Jean-Pierre Brion, Kunie Ando
Summary: AHN plays a critical role in sustaining hippocampal functions such as learning and memory, and impaired AHN in AD patients may contribute to cognitive deficits. NFTs and amyloid plaques are key neuropathological hallmarks of AD, with abnormal tau protein accumulation impacting AHN. Further research is needed to fully understand the relationship between tau pathology and AHN.
FRONTIERS IN NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Zihan Qi, Ying Zhang, Kai Yao, Mengqi Zhang, Yixuan Xu, Jianfeng Zhang, Xiaojing Bai, Hengbing Zu
Summary: Downregulation of DHCR24 may be associated with the pathogenesis of AD, affecting tau protein phosphorylation and cholesterol synthesis, as demonstrated in a novel lipid raft-dependent PP2A signaling pathway.
NEUROCHEMICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Marta Sidoryk-Wegrzynowicz, Beata Dabrowska-Bouta, Grzegorz Sulkowski, Lidia Struzynska
Summary: Tau-dependent neurodegeneration in a transgenic mouse model is accompanied by astrocytosis, indicating the critical role of astrocytes in the disease development. Alterations in glutamine transport and recycling affect the neuronal-astrocytic integrity, suggesting potential mechanisms operating in Tau pathology.
NEUROCHEMISTRY INTERNATIONAL
(2023)
Review
Cell Biology
Geraldine Zimmer-Bensch, Hans Zempel
Summary: Tauopathies, including Alzheimer's Disease, are common neurological disorders that primarily affect the aging population, but can also impact children and young adults. Characterized by cognitive dysfunction and movement abnormalities, these diseases can lead to severe neurological deficits and premature death. Genetic and epigenetic factors play a role in the etiology of tauopathies, with potential diagnostic and therapeutic implications.
Article
Neurosciences
Patricia Morcillo, Hector Cordero, Omamuyovwi M. Ijomone, Akinyemi Ayodele, Julia Bornhorst, Leslie Gunther, Frank P. Macaluso, Aaron B. Bowman, Michael Aschner
Summary: The study found that manganese can disrupt mitochondrial dynamics by affecting mitochondrial fission and fusion, leading to impaired respiratory capacity and structure of mitochondria. It also interferes with mitochondrial trafficking and communication, which may be a common pathway underlying neurodegenerative diseases.
MOLECULAR NEUROBIOLOGY
(2021)
Review
Biology
Parisa Tabeshmehr, Eftekhar Eftekharpour
Summary: Tau is a critical protein for maintaining the structure and function of nerve cells. Changes in tau have been linked to many diseases, but there are significant differences in tau modifications among these diseases. This review provides an overview of tau physiology and pathophysiology in neurodegenerative diseases and discusses current diagnostic and therapeutic approaches. It is aimed at enhancing the understanding of graduate students specializing in neurobiology.
Article
Neurosciences
Sanming Li, Ethan R. Roy, Yanyu Wang, Trent Watkins, Wei Cao
Summary: Alzheimer's disease is a neurodegenerative disorder, and tau aggregation is closely linked to its clinical progression. This study overexpressed human tau in primary mouse neurons and observed significant axonal degeneration and cell death, providing convincing evidence for the association between tau-induced neurodegeneration and AD.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Endocrinology & Metabolism
Jing Xiong, Isaac Deng, Sally Kelliny, Liying Lin, Larisa Bobrovskaya, Xin-Fu Zhou
Summary: This study investigates the effects of high fat diet-induced obesity on tau phosphorylation and its relationship with Alzheimer's disease and type 2 diabetes. The results suggest that diet-induced obesity exacerbates tau pathology and induces T2DM in transgenic mice expressing the P301L mutant human tau, providing a useful model for investigating the underlying biochemical changes and mechanisms associated with metabolic disorders and AD tauopathy.
METABOLIC BRAIN DISEASE
(2022)
Review
Neurosciences
Marta Caamano-Moreno, Ricardo Gargini
Summary: This article discusses the impact of aberrant aggregation of tau protein in neurons and glia on synaptic dysfunctions, leading to cognitive symptoms. The mechanisms affected by tau protein inclusions in neurons, astrocytes, and oligodendrocytes are evaluated. This is of great importance for understanding and treating tauopathies.
Article
Medicine, Research & Experimental
Minji Kim, Hiroaki Sekiya, Gary Yao, Nicholas B. Martin, Monica Castanedes-Casey, Dennis W. Dickson, Tae Hyun Hwang, Shunsuke Koga
Summary: Neuropathologic assessment during autopsy is the gold standard for diagnosing neurodegenerative disorders. In this study, a weakly supervised deep learning-based approach called clustering-constrained-attention multiple-instance learning (CLAM) was used to develop a pipeline for diagnosing Alzheimer's disease (AD) and other tauopathies. The multiattention-branch CLAM model achieved the highest diagnostic accuracy for classifying neurodegenerative disorders. This study supports the feasibility of deep learning-based approaches for the classification of neurodegenerative disorders on whole-slide images (WSIs).
LABORATORY INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
S. Pankivskyi, D. Pastre, E. Steiner, V Joshi, A. Rynditch, L. Hamon
Summary: SAM68 is an mRNA-binding protein involved in mRNA processing in the nucleus, and its interaction with ITSN1 can enhance its solubility, regulating the processing of a fraction of nuclear mRNAs. ITSN1 and mRNA may act together to promote SAM68 solubilization, which is important for SAM68-controlled splicing events related to higher neuronal functions or cancer progression.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biology
Anastasiia Samsonova, Krystel El Hage, Benedicte Desforges, Vandana Joshi, Marie-Jeanne Clement, Guillaume Lambert, Helene Henrie, Nicolas Babault, Pierrick Craveur, Rachid C. Maroun, Emilie Steiner, Ahmed Bouhss, Alexandre Maucuer, Dmitry N. Lyabin, Lev P. Ovchinnikov, Loic Hamon, David Pastre
Summary: Samsonova et al. demonstrate a cooperative association of Lin28 and YB-1 for target mRNA through their cold-shock domain, suggesting that this association may contribute to translational plasticity during development and adaptation of cancer cells to adverse environments.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Asaki Kobayashi, Marie-Jeanne Clement, Pierrick Craveur, Krystel El Hage, Jean de Matha Salone, Guillaume Bollot, David Pastre, Alexandre Maucuer
Summary: Splicing factor mutations are common in various cancers, and cells with these mutations are vulnerable to certain drugs. Through virtual screening and experimental validation, researchers discovered a small molecule, UHMCP1, that can disrupt specific splicing factor interactions, affecting RNA splicing and cell viability.
Article
Biochemistry & Molecular Biology
Karina Budkina, Krystel El Hage, Marie-Jeanne Clement, Benedicte Desforges, Ahmed Bouhss, Vandana Joshi, Alexandre Maucuer, Loic Hamon, Lev P. Ovchinnikov, Dmitry N. Lyabin, David Pastre
Summary: The study reveals that YB-1 can unwind mRNA secondary structures under cellular stress by utilizing its cold-shock domain and C-terminal domain. YB-1 aids in stress granule disassembly during recovery, and its overexpression inhibits stress granule assembly in cancer cells by promoting mRNA translation initiation.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Cell Biology
Fred Bernard, Julie Jouette, Catherine Durieu, Remi Le Borgne, Antoine Guichet, Sandra Claret
Summary: A new method has been developed in cell biology to detect GFP fusion proteins efficiently by combining a nanobody anti-GFP (GBP) with APEX, without the need for specific antibodies or generation of additional constructions. This tool has been successfully used to detect various proteins in Drosophila ovarian follicles, showcasing its feasibility and efficiency. The method was further optimized by expressing the tool in Drosophila using the UAS/GAL4 system for spatiotemporal control of protein detection.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Jing Xie, Javad Najafi, Remi Le Borgne, Jean-Marc Verbavatz, Catherine Durieu, Jeremy Salle, Nicolas Minc
Summary: Cells are filled with macromolecules and polymer networks that provide viscous and elastic properties to the cytoplasm. Using magnetic tweezers, researchers found that the cytoplasm can exert reactive forces to move organelles back to their original positions. These findings have important implications for cell division positioning and cellular organization.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Noemie Gaudin, Paula Martin Gil, Meriem Boumendjel, Dmitry Ershov, Catherine Pioche-Durieu, Manon Bouix, Quentin Delobelle, Lucia Maniscalco, Than Bich Ngan Phan, Vincent Heyer, Bernardo Reina-San-Martin, Juliette Azimzadeh
Summary: Rotationally asymmetric molecular features have been discovered in human centrioles, which are crucial for primary ciliogenesis and ciliary signaling.
Article
Multidisciplinary Sciences
Irma Custovic, Nicolas Pocholle, Eric Bourillot, Eric Lesniewska, Olivier Pietrement
Summary: Significant efforts have been made in the past two decades to develop nanoscale spectroscopy techniques for single-molecule structural detection and to address questions in heterogeneous biological systems. While the application of infrared atomic force microscopy (AFM-IR) has been successful in obtaining absorption spectra with nanoscale spatial resolution for proteins, studying DNA molecules on surfaces using AFM-IR remains challenging. In this study, we demonstrate a methodological approach to acquire AFM-IR mapping modalities with corresponding absorption spectra using two different DNA deposition protocols. We show the nanoscale infrared absorbance of distinct DNA morphologies on surfaces through a series of AFM-IR absorption maps with corresponding infrared spectra. Our results highlight the sensitivity of AFM-IR nanospectroscopy in nucleic acid research and its potential in further investigations of nucleoprotein complexes.
SCIENTIFIC REPORTS
(2022)
Article
Biology
Krystel El Hage, Nicolas Babault, Olek Maciejak, Benedicte Desforges, Pierrick Craveur, Emilie Steiner, Juan Carlos Rengifo-Gonzalez, Helene Henrie, Marie-Jeanne Clement, Vandana Joshi, Ahmed Bouhss, Liya Wang, Cyril Bauvais, David Pastre
Summary: RNA-protein interactions (RPIs) hold promise as therapeutic targets, but lack of methods and feedback between computational and experimental techniques hampers drug discovery. In this study, we address these challenges by developing an approach that combines computational techniques and cell-based scoring to identify small RPI inhibitors, focusing on the Y-box binding protein 1 (YB-1). We validated 22 hits using molecular dynamics simulations and nuclear magnetic resonance spectroscopy, and found that 11 significantly interfere with mRNA binding to YB-1 in cells. One of the leads is an FDA-approved PARP-1 inhibitor. This work demonstrates the potential of our integrative approach for rational development of RPI inhibitors.
Article
Chemistry, Multidisciplinary
David Adame Brooks, Olivier Pietrement, Elodie Dardillac, Ayesha Jayantha, Manuel A. Lores Guevara, Fidel Antonio Castro-Smirnov, Pilar Aranda, Eduardo Ruiz-Hitzky, Bernard S. Lopez
Summary: Research shows that sonication can improve the dispersion performance of sepiolite, a naturally occurring clay silicate, and enhance its interaction with biomacromolecules such as bovine serum albumin. Sonication also reduces the toxicity of sepiolite in mammalian cells.
Article
Biology
Binita Goswami, Deepika Ahuja, David Pastre, Partho Sarothi Ray
Summary: Post-transcriptional regulation of p53, controlled by miR-125b and HuR, determines its expression in response to DNA damage. miR-125b represses p53 mRNA translation, while its reduction upon DNA damage relieves the repression, leading to pulsatile expression of p53. The decrease in miR-125b level is caused by enhanced exosomal export mediated by HuR, while the subsequent increase is due to p53-mediated transcriptional upregulation and enhanced processing. The reciprocal feedback loops between miR-125b and p53 contribute to the fine-tuned temporal regulation of p53 expression.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Aleix Tarres-Sole, Federica Battistini, Joachim M. Gerhold, Olivier Pietrement, Belen Martinez-Garcia, Elena Ruiz-Lopez, Sebastien Lyonnais, Pau Bernado, Joaquim Roca, Modesto Orozco, Eric Le Cam, Juhan Sedman, Maria Sola
Summary: A new mechanism of mitochondrial DNA compaction was discovered, in which the Gcf1p protein in Candida albicans utilizes its multiple domains to connect co-aligned DNA segments without altering DNA topology.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Evgeniya M. Mamontova, Marie-Jeanne Clement, Maria V. Sukhanova, Vandana Joshi, Ahmed Bouhss, Juan Carlos Rengifo-Gonzalez, Benedicte Desforges, Loic Hamon, Olga I. Lavrik, David Pastre
Summary: In this study, it was discovered that the RNA-binding protein FUS is directed to PAR through its RNA recognition motif, enhancing PAR synthesis. Specific residues in the FUS RRM were found to be PARylated by PARP-1 to control PAR synthesis levels. A model was proposed where FUS is released from nascent mRNA during transcriptional arrest and recruited by DNA-damage activated PARP-1 to stimulate PAR synthesis. This model offers new perspectives on the role of FET proteins in cancers and neurodegenerative diseases.
