Article
Biochemistry & Molecular Biology
Mahamat Babagana, Lorin R. Brown, Hannah Z. Slabodkin, Julia V. Kichina, Eugene S. Kandel
Summary: Hyperactivity of AKT in cancer cells leads to increased sensitivity to proteotoxic stress, manifested by heightened response to heat shock and greater dependence on XBP1 for growth. This stress-induced vulnerability can be exploited for therapeutic targeting.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Neurosciences
Maria Elena Pero, Farihah Chowdhury, Francesca Bartolini
Summary: Peripheral neuropathy is a common disorder resulting from nerve damage in the periphery. The degeneration of sensory axon terminals leads to changes in sensory functions, causing pain, weakness, numbness, tingling, and disability. Tubulin damage has been identified as a potential underlying mechanism for various peripheral neuropathies, and post-translational modifications of tubulin have been implicated in the regulation of axonal transport and mitochondria dynamics.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Multidisciplinary Sciences
Marco D. Carpenter, Delaney K. Fischer, Shuo Zhang, Allison M. Bond, Kyle S. Czarnecki, Morgan T. Woolf, Hongjun Song, Elizabeth A. Heller
Summary: The authors optimized a hybrid protocol, ICuRuS, to profile epigenetic features in neuronal subtypes from a single mouse. This method allows for robust epigenetic profiling at cell-type specific resolution.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Jing Du, Shu-Kai Li, Liu-Yuan Guan, Zheng Guo, Jiang-Fan Yin, Li Gao, Toru Kawanishi, Atsuko Shimada, Qiu-Ping Zhang, Li-Sha Zheng, Yi-Yao Liu, Xi-Qiao Feng, Lin Zhao, Dong-Yan Chen, Hiroyuki Takeda, Yu-Bo Fan
Summary: This study reveals that heat shock factor 1 (HSF1) is asymmetrically activated in the presence of nodal flow in zebrafish embryos. Deficiency in HSF1 expression leads to situs inversus and disrupted gene expression asymmetry of nodal signaling proteins. Additionally, cilia and Ca(2+) Akt signaling axis are crucial for the activation of HSF1 under mechanical stress.
Review
Neurosciences
Cecilia Rocha, Panagiotis Prinos
Summary: Primary cilia play a critical role in directing cellular signaling events during brain development and neuronal differentiation. Genetic and epigenetic alterations, as well as RNA processing and post-translational modifications, contribute to the development of human neuronal disorders and brain tumors. This review summarizes research on mouse and human studies of ciliogenesis and primary cilia function in the brain, highlighting their role in maintaining neuronal progenitor populations, coordinating neuronal differentiation, and controlling key signaling pathways critical for neurogenesis. The impact of post-translational modifications and missplicing of ciliary genes leading to ciliopathies and cell cycle alterations is also discussed. Ultimately, genetic and epigenetic studies of cilia shed light on the cellular and molecular mechanisms underlying neurodevelopmental disorders and brain tumors.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Biology
Bothina Mohammed Alharbi, Tahani H. Albinhassan, Razan Ali Alzahrani, Abderrezak Bouchama, Sameer Mohammad, Awatif Abdulaziz Alomari, May Nasser Bin-Jumah, Entissar S. AlSuhaibani, Shuja Shafi Malik
Summary: Rising temperatures and heat waves caused by climate change are detrimental to human health. Exposure to extreme heat during heat waves can cause heat-related illnesses, including heat stroke, which can result in permanent disability. Heat can damage proteins, leading to their misfolding and aggregation, which can be neurotoxic and contribute to neurodegenerative disorders.
Review
Pharmacology & Pharmacy
Jose Torres-Perez, Jahanzaib Irfan, Muhammad Rizki Febrianto, Simone Di Giovanni, Istvan Nagy
Summary: The article discusses the role of histone post-translational modifications (PTMs) in influencing nociception and pain phenotypes following tissue injury, and the opportunities and challenges of targeting histone PTMs to relieve pain in clinically relevant tissue injuries.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Alec Santiago, Kevin A. Morano
Summary: Neurodegenerative diseases are linked to protein damage caused by oxidative stress. The Hsp70 chaperone family plays a key role in protein misfolding management, and its function can be modulated by modifying cysteines in the ATPase domain. This study investigates the consequences of cysteine modification on the Hsp70 Ssa1 in yeast and reveals the importance of Hsp70 in oxidative stress and proteostasis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Neurosciences
Rong Liu, Wei Dong, Dan Xiong, Lanqi Hu, Haoran Zhang, Xiaoping Yuan, Zhonghui Tang, Fang Fu, Xin Yang, Xia Wu
Summary: This study cultured fetal prefrontal cortical tissues and found that at gestation weeks 11 and 20, there were predominantly excitatory and inhibitory neurons, respectively. The abrupt transition in cell proportions was due to the differential lineage specificity of neural progenitors in the fetal cortical tissues at different stages of fetal brain development. Additionally, the transcriptional profiles of cultured fetal cortical tissues were strongly influenced by the presence of FGF2.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Food Science & Technology
Xiang Gao, Miao Yu, Wenchang Sun, Yarao Han, Jinghua Yang, Xiaobo Lu, Cuihong Jin, Shengwen Wu, Yuan Cai
Summary: Autophagy is a lysosome dependent degradation pathway in eukaryotic cells that plays a crucial role in cell balance and survival. Lanthanum (La), a rare earth element, has been shown to induce abnormal autophagy in rat hippocampus by affecting signaling pathways, leading to neuronal damage.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Review
Cell Biology
Olga G. Zatsepina, Michael B. Evgen'ev, David G. Garbuz
Summary: Hsp70, a class of molecular chaperones, plays a crucial role in protecting neurons from various stresses, aiding in memory formation by facilitating protein folding and transport at synapses, modulating signaling cascades, and participating in neurotransmitter release mechanisms. Moreover, Hsp70 shows significant protective potential in neurodegenerative diseases, reducing neurodegeneration, stimulating neurogenesis, and restoring memory. These findings suggest that recombinant Hsp70 and Hsp70 pharmacological inducers could serve as potential drugs for treating ischemic injury and neurodegenerative disorders.
Article
Biochemistry & Molecular Biology
Vsevolod Pinelis, Irina Krasilnikova, Zanda Bakaeva, Alexander Surin, Dmitrii Boyarkin, Andrei Fisenko, Olga Krasilnikova, Igor Pomytkin
Summary: Insulin decreases the production of intracellular and mitochondrial superoxide anion (O-2(-center dot)) in glutamate-induced excitotoxicity and reduces the delayed calcium deregulation (DCD). The NMDAR inhibitor MK 801 completely eliminates the effects of glutamate.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Clement E. Lemercier, Andre Garenne, Florence Poulletier de Gannes, Corinne El Khoueiry, Delia Arnaud-Cormos, Philippe Leveque, Isabelle Lagroye, Yann Percherancier, Noelle Lewis
Summary: Previous studies have shown that cortical neuron networks grown on microelectrode arrays are sensitive to radiofrequency (RF) fields and exhibit increased inhibitory response with longer exposure and higher power. This study aimed to compare the inhibitory effect of RF fields to the gamma-aminobutyric acid type A (GABA(A)) receptor agonist muscimol (MU). The results showed that RF exposure inhibited network bursting activity at a specific SAR level and had a smaller effect on bursting synchrony compared to MU. Network rebound excitation was observed after MU washout but not after RF exposure, suggesting that RF fields do not rely on hyperpolarization for inhibition. At the single neuron level, both RF fields and MU reduced action potential (AP) half-width, which may contribute to the reduction in network bursting activity. These findings suggest that the inhibitory mechanisms of RF fields differ from those mediated by GABA(A) receptors.
Article
Neurosciences
Marina A. Ayad, Timothy Mahon, Mihir Patel, Marina M. Cararo-Lopes, Ilker Hacihaliloglu, Bonnie L. Firestein, Nada N. Boustany
Summary: This study demonstrates the use of the vinculin tension sensor (VinTS) in primary cultures of cortical neurons to study the interaction between neurons and mechanical forces. The results show that vinculin is under low tension in growth cones and its FRET efficiency is more sensitive to growth cone dynamics compared to a control sensor. This study provides a foundation for further investigations of mechanotransduction in neurons using VinTS.
Article
Engineering, Biomedical
Ines Dias, Marloes R. Levers, Martina Lamberti, Gerco C. Hassink, Richard van Wezel, Joost le Feber
Summary: In the study, it was found that cortical neurons in rat cultures displayed network bursts in the absence of cholinergic input, while cultures with high cholinergic tone showed reduced network excitability and dispersed firing. Electrical stimulation could alter connectivity, but repeated stimuli no longer had the same effect.
JOURNAL OF NEURAL ENGINEERING
(2021)
Article
Nanoscience & Nanotechnology
Pablo Cabrera, Pedro Jara-Guajardo, Maria Paz Oyarzun, Nicole Parra-Munoz, Aldo Campos, Monica Soler, Alejandra Alvarez, Francisco Morales-Zavala, Eyleen Araya, Alicia N. Minniti, Rebeca Aldunate, Marcelo J. Kogan
Summary: This study demonstrates an improved detection of A beta aggregates in C. elegans and mouse models of AD by co-administering functionalized gold nanorods with fluorescent probes, suggesting the potential of using plasmonic gold nanoparticles to enhance the detection of A beta in vivo.
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
(2022)
Article
Cell Biology
Nicola Guzzi, Sowndarya Muthukumar, Maciej Ciesla, Gabriele Todisco, Phuong Cao Thi Ngoc, Magdalena Madej, Roberto Munita, Serena Fazio, Simon Ekstrom, Teresa Mortera-Blanco, Monika Jansson, Yasuhito Nannya, Mario Cazzola, Seishi Ogawa, Luca Malcovati, Eva Hellstrom-Lindberg, Marios Dimitriou, Cristian Bellodi
Summary: This study demonstrates that pseudouridylation of a stem cell-enriched tRF subtype, mini tRFs containing a 5' terminal oligoguanine (mTOG), selectively inhibits aberrant protein synthesis programs, thereby promoting engraftment and differentiation of hematopoietic stem and progenitor cells in MDS patients. The mechanism involves hindering the recruitment of translational co-activator PAIP1 and repressing translation of transcripts sharing pyrimidine-enriched sequences at the 5' UTR, including TOP sequences frequently altered in cancer. Dysregulation of mTOG leads to increased translation of 5' PES mRNA in malignant MDS-HSPCs, which is associated with leukaemic transformation and reduced patient survival.
NATURE CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Carlos Rivera, Hun-Goo Lee, Anna Lappala, Danni Wang, Veronica Noches, Montserrat Olivares-Costa, Marcela Sjoberg-Herrera, Jeannie T. Lee, Maria Estela Andres
Summary: RCOR1 is paradoxically enriched in transcriptionally active chromatin and represses transcription through two mechanisms.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Ilias Georgakopoulos-Soares, Guillermo E. Parada, Hei Yuen Wong, Ragini Medhi, Giulia Furlan, Roberto Munita, Eric A. Miska, Chun Kit Kwok, Martin Hemberg
Summary: This study reveals the enrichment of G4 motifs near splice junctions, suggesting their regulatory role in RNA stability and splicing. G4 motifs play important roles in exon skipping and inclusion, and are associated with multiple RNA binding proteins. Furthermore, G4 motifs show strong enrichment at splice sites in mammals and birds, indicating the evolutionary conservation of this splice regulatory mechanism.
NATURE COMMUNICATIONS
(2022)
Review
Immunology
Daniela Elgueta, Paola Murgas, Erick Riquelme, Guang Yang, Gonzalo I. Cancino
Summary: Infections during pregnancy can have serious consequences for fetal neurodevelopment, leading to neurodevelopmental disorders such as autism spectrum disorder and cognitive impairment. The mechanisms behind these effects may involve aberrant activation of the maternal immune system, leading to inflammation and direct infection of fetal neural cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Rafaella V. Zarate, Sergio Hidalgo, Nicole Navarro, Daniela Molina-Mateo, Duxan Arancibia, Francisca Rojo-Cortes, Carlos Oliva, Maria Estela Andres, Pedro Zamorano, Jorge M. Campusano
Summary: Parkinson's disease (PD) is a neurodegenerative disease characterized by motor symptoms and dopaminergic cell loss. This study shows that early dysfunction in the serotonergic system precedes and contributes to the onset of the Parkinsonian phenotype in Drosophila PD model. Manipulating the serotonergic system early on can prevent dopaminergic neuron loss and improve motor impairment.
Article
Cell Biology
Tamara Marin, Andres E. Dulcey, Fabian Campos, Catalina de la Fuente, Mariana Acuna, Juan Castro, Claudio Pinto, Maria Jose Yanez, Cristian Cortez, David W. McGrath, Pablo J. Saez, Kirill Gorshkov, Wei Zheng, Noel Southall, Maria Carmo-Fonseca, Juan Marugan, Alejandra R. Alvarez, Silvana Zanlungo
Summary: Niemann-Pick type A (NPA) disease is a fatal lysosomal neurodegenerative disorder. Recent studies have shown that c-Abl tyrosine kinase activity plays a role in neuronal damage and death in NPA disease. There is potential for the use of c-Abl inhibitors in the clinical treatment of NPA patients.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Fredrik Salmen, Joachim De Jonghe, Tomasz S. Kaminski, Anna Alemany, Guillermo E. Parada, Joe Verity-Legg, Ayaka Yanagida, Timo N. Kohler, Nicholas Battich, Floris van den Brekel, Anna L. Ellermann, Alfonso Martinez Arias, Jennifer Nichols, Martin Hemberg, Florian Hollfelder, Alexander van Oudenaarden
Summary: VASA-seq is a method that can detect the total transcriptome in single cells by fragmenting and tailing all RNA molecules after cell lysis. It is compatible with different experimental formats and can be used to analyze cell type markers, in vivo cell cycle, and alternative splicing, among others.
NATURE BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
K. Pimkova, M. Jassinskaja, R. Munita, M. Ciesla, N. Guzzi, P. Cao Thi Ngoc, M. Vajrychova, E. Johansson, C. Bellodi, J. Hansson
Summary: Fetal and adult hematopoietic stem and progenitor cells have distinct redox homeostasis, with fetal cells being more susceptible to protein thiol oxidation. The study reveals ontogenic changes to oxidation state of thiols in proteins involved in metabolism and protein homeostasis, as well as thiol oxidation changes in mitochondrial respiration and protein homeostasis during initiation of MLL-rearranged leukemia in fetal hematopoietic stem and progenitor cells.
Article
Biochemistry & Molecular Biology
Juan Zegers-Delgado, Alejandro Aguilera-Soza, Florencia Calderon, Harley Davidson, Daniel Verbel-Vergara, Hector E. Yarur, Javier Novoa, Camila Blanlot, Cristian P. Bastias, Maria Estela Andres, Katia Gysling
Summary: The study found that the control of neurotransmission by CRF receptors in the NAc is influenced by life stage. In adult rats, the CRF-R1 antagonist decreased DA levels and increased glutamate levels in response to a depolarizing stimulus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
America Chandia-Cristi, Nicolas Stuardo, Cristian Trejos, Nancy Leal, Daniela Urrutia, Francisca C. Bronfman, Alejandra Alvarez Rojas
Summary: Brain-derived neurotrophic factor (BDNF) activates TrkB receptor and downstream pathways, promoting neuronal survival, growth, and plasticity. The role of c-Abl, a non-receptor tyrosine kinase, in BDNF-induced dendritic arborization was examined using various strategies. Surprisingly, BDNF promoted c-Abl activation and interaction with TrkB receptors. Inhibition or genetic ablation of c-Abl abolished BDNF-induced dendritic arborization without affecting classic TrkB downstream pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Daniela A. Gutierrez, America Chandia-Cristi, Maria Jose Yanez, Silvana Zanlungo, Alejandra R. Alvarez
Summary: This review focuses on the role of the non-receptor tyrosine kinase c-Abl in synaptic and neuronal functions. It has been found that the activation of c-Abl can be detrimental to neurons and may promote the development of neurodegenerative diseases. However, c-Abl activity plays a pivotal role in healthy synaptic plasticity, dendritic spine remodeling, and gene expression regulation after cognitive training.
NEURAL REGENERATION RESEARCH
(2023)
Article
Multidisciplinary Sciences
Benjamin Cartes-Saavedra, Daniel Lagos, Josefa Macuada, Duxan Arancibia, Florence Burte, Marcela K. Sjoberg-Herrera, Maria Estela Andres, Rita Horvath, Patrick Yu-Wai-Man, Gyorgy Hajnoczky, Veronica Eisnera
Summary: The fusion and shape of the inner mitochondrial membrane rely on the protein OPA1. Mutations in OPA1 cause autosomal dominant optic atrophy (ADOA), a significant cause of inherited blindness. The specific roles of the GTPase and GED domains of OPA1 in mitochondrial fusion and cristae shape are still unclear.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Geriatrics & Gerontology
Rilda Leon, Daniela A. Gutierrez, Claudio Pinto, Cristian Morales, Catalina de la Fuente, Cristobal Riquelme, Bastian I. Cortes, Adrian Gonzalez-Martin, David Chamorro, Nelson Espinosa, Pablo Fuentealba, Gonzalo I. Cancino, Silvana Zanlungo, Andres E. Dulcey, Juan J. Marugan, Alejandra Alvarez Rojas
Summary: The study explores the role of c-Abl kinase in Alzheimer's disease (AD), using the APP/PS1 mouse model. The results demonstrate that the absence or inhibition of c-Abl improves cognitive performance in AD mice, with reduced amyloid plaques and preserved neurons in the hippocampus. These findings suggest that c-Abl could be a potential target for AD therapies.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Alexis Martinez, Cristian M. Lamaizon, Cristian Valls, Fabien Llambi, Nancy Leal, Patrick Fitzgerald, Cliff Guy, Marcin M. Kaminski, Nibaldo C. Inestrosa, Brigitte van Zundert, Gonzalo I. Cancino, Andres E. Dulcey, Silvana Zanlungo, Juan J. Marugan, Claudio Hetz, Douglas R. Green, Alejandra R. Alvarez
Summary: Endoplasmic reticulum stress activates c-Abl tyrosine kinase, which translocates to mitochondria. Activated c-Abl interacts with mitochondrial fusion protein MFN2, leading to mitochondrial fragmentation and apoptosis.