Article
Biochemistry & Molecular Biology
Lisa A. Walter, Lauren P. Blake, Yann S. Gallot, Charles J. Arends, Randall S. Sozio, Stephen M. Onifer, Kyle R. Bohnert
Summary: This study investigates the molecular mechanisms controlling skeletal muscle atrophy following denervation. It shows that transection of the sciatic nerve leads to significant skeletal muscle atrophy in rats, while having little effect on the neuromuscular junction. The study also reveals the activation of the unfolded protein response in denervated skeletal muscle, with ATF4 and ATF6 elevated in the cytoplasm and XBP1 elevated in the nuclei. These findings suggest a potential role of the unfolded protein response and XBP1 in maintaining skeletal muscle and the neuromuscular junction after peripheral nerve injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Irene Casola, Bianca Maria Scicchitano, Elisa Lepore, Silvia Mandillo, Elisabetta Golini, Carmine Nicoletti, Laura Barberi, Gabriella Dobrowolny, Antonio Musaro
Summary: This study analyzed the expression levels of two myomiRs in different contexts, including ALS disease and denervation models. The results showed that miR-206 and miR-133a exhibit different expression patterns in ALS disease and nerve regeneration processes, which are important for understanding the pathogenesis and treatment of ALS.
Article
Cell Biology
Marta Montori-Grau, David Aguilar-Recarte, Mohammad Zarei, Javier Pizarro-Delgado, Xavier Palomer, Manuel Vazquez-Carrera
Summary: This study found that endoplasmic reticulum (ER) stress downregulates the expression of PGC-1 alpha in skeletal muscle through the activation of ATF4 and the mTOR-CRTC2 pathway. These findings suggest that inhibition of ATF4 and the mTOR-CRTC2 axis could be a therapeutic target for insulin resistant states.
CELL COMMUNICATION AND SIGNALING
(2022)
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)
Article
Biochemistry & Molecular Biology
Hayden W. Hyatt, Mustafa Ozdemir, Toshinori Yoshihara, Branden L. Nguyen, Rafael Deminice, Scott K. Powers
Summary: Mechanical ventilation is a life-saving intervention for critically ill patients, but it can lead to ventilator-induced diaphragm dysfunction (VIDD) due to oxidative stress activating major proteolytic systems. Calpain activation plays an essential role in VIDD development, leading to oxidative stress, muscle atrophy, and contractile dysfunction.
Article
Biochemistry & Molecular Biology
Anna Kowalczuk, Nabila Bourebaba, Juliia Panchuk, Krzysztof Marycz, Lynda Bourebaba
Summary: This study investigates the effects of calystegines on human adipose-derived stem cells (HuASCs) in an experimentally induced hyperglycemic model. The results demonstrate that calystegines promote the survival of hyperglycemic cells and decrease oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum stress. Additionally, calystegines prevent the hyperglycemia-induced inflammatory response and restore the defective PI3K/AKT/mTOR pathway, thus improving metabolic functions of HuASCs cells.
Article
Cell Biology
Sung Woo Choi, Heeseung Oh, Seung Yeon Park, Wonjun Cho, A. M. Abd El-Aty, Ahmet Hacimuftuoglu, Ji Hoon Jeong, Tae Woo Jung
Summary: Gremlin-1 (GR1) is a novel adipokine that is highly expressed in human adipocytes and has been shown to inhibit the BMP2/4-TGFβ signaling pathway, leading to insulin resistance in skeletal muscle, adipocytes, and hepatocytes. This study investigated the effect of GR1 on hepatic lipid metabolism and found that it promotes hepatic ER stress, lipid accumulation, and lipogenesis, while reducing autophagy. Targeting GR1 could be a potential therapeutic approach for metabolic diseases, including MAFLD.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Food Science & Technology
Jie Yang, Shibo Bao, Shengxiang Luo, Liping Jiang, Qiujuan Li, Ying Kong, Jun Cao, Jun Cao
Summary: Curcumin inhibits both autophagy and the mTOR pathway, and they both play a significant role in suppressing the growth of A549 cells. Blocking ATF4 reduces the expression of autophagy-related proteins and AKT/mTOR. Curcumin can effectively reduce the weight and volume of transplanted tumors in mice.
FOOD AND CHEMICAL TOXICOLOGY
(2023)
Article
Geriatrics & Gerontology
Theresa Mader, Thomas Chaillou, Estela Santos Alves, Baptiste Jude, Arthur J. Cheng, Ellinor Kenne, Sara Mijwel, Ewa Kurzejamska, Clara Theresa Vincent, Helene Rundqvist, Johanna T. Lanner
Summary: Patients with breast cancer often experience muscle weakness, which is associated with increased mortality risk and reduced quality of life. Even in the absence of muscle mass loss, breast cancer patients can still have intrinsic muscle dysfunction. The molecular processes underlying breast cancer-induced muscle weakness and the beneficial effect of exercise are not well understood.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2022)
Review
Biochemistry & Molecular Biology
Yann S. Gallot, Kyle R. Bohnert
Summary: Skeletal muscle is a highly plastic tissue capable of adapting to various stimuli, with ER stress and activation of the unfolded protein response (UPR) being induced under conditions such as exercise, hypoxia, and calcium imbalances. The UPR in skeletal muscle is still being elucidated, as evidence suggests its involvement in various catabolic stimuli and potential roles in maintaining homeostasis or driving atrophy. Continued investigations into the individual molecules of this complex pathway are crucial for a full understanding of the mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Julliane Tamara Araujo de Melo Campos, Jorge Luiz Dantas de Medeiros, Maria Eduarda Cardoso de Melo, Monique Alvares da Silva, Matheus Oliveira de Sena, Aquiles Sales Craveiro Sarmento, Lucymara Fassarella Agnez Lima, Guilherme Augusto de Freitas Fregonezi, Josivan Gomes Lima
Summary: Lipodystrophy syndromes are rare diseases related to adipose tissue impairment and metabolic comorbidities; they can be categorized as partial or generalized, inherited or acquired, and are associated with redox, ER homeostasis, and muscle dysfunction.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Oncology
Ruoheng Zhang, J. D. Neighbors, T. D. Schell, R. J. Hohl
Summary: MeSG treatment induces immunogenic cell death by exposing CRT on the cell surface and enhancing phagocytosis by dendritic cells. Unlike the canonical pathway, MeSG does not cause ER stress and does not require PERK to induce CRT exposure.
Review
Cell Biology
Jesus Burillo, Patricia Marques, Beatriz Jimenez, Carlos Gonzalez-Blanco, Manuel Benito, Carlos Guillen
Summary: This review examines the main molecular mechanisms that may be involved in the connection between type 2 diabetes and neurodegenerative diseases, with a focus on inflammation, endoplasmic reticulum stress, autophagy, and mitochondrial dysfunction.
Article
Pharmacology & Pharmacy
Amal Kamal Abdel-Aziz, Eman M. E. Dokla, Khaled A. M. Abouzid, Saverio Minucci
Summary: This study discovered a novel endoplasmic reticulum (ER) inducer, EMD37, which exhibited potent anticancer activity against NCI-60 cancer cell lines. Genome-wide transcriptome profiling and drug signature mining revealed that EMD37 promoted ER stress and unfolded protein response (UPR) mechanisms. Additionally, EMD37 inhibited mTOR signaling and induced G2/M cell cycle arrest and apoptosis in human cancer cells.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Dongjian Han, Fuhang Wang, Bo Wang, Zhentao Qiao, Xinyue Cui, Yi Zhang, Qingjiao Jiang, Miaomiao Liu, Jiahong Shangguan, Xiaohui Zheng, Yajun Bai, Chunyan Du, Deliang Shen
Summary: Tanshinol borneol ester (DBZ) has been shown to have anti-atherosclerotic and anti-inflammatory effects, but its effects on cardiac hypertrophy are not well understood. This study found that DBZ inhibited oxidative stress and ER stress, blocked autophagy flow, and decreased apoptosis by regulating the mTOR/β-TrcP/NRF2 signal pathway, suggesting that it may be a promising therapeutic approach for stress-induced cardiac hypertrophy.
FRONTIERS IN PHARMACOLOGY
(2022)
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)
Article
Neurosciences
Claire Pleau, Angelique Peret, Edouard Pearlstein, Thomas Scalfati, Alexandre Vigier, Geoffrey Marti, Francois J. Michel, Thomas Marissal, Valerie Crepel
Summary: Research has found that DGCs recruited in the home cage condition are mature neurons with longer dendritic trees and lower excitability. The higher GABA(A) receptor-mediated shunting inhibition contributes to the lower excitability of DGCs activated in the home environment.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Batoul Chouaib, Pierre-Yves Collart-Dutilleul, Nicolas Blanc-Sylvestre, Richard Younes, Csilla Gergely, Cedric Raoul, Frederique Scamps, Frederic Cuisinier, Olivier Romieu
Summary: Stem cell-derived conditioned media show promise as pharmaceutical products for tissue regeneration, with human dental pulp cells (DPCs) conditioned medium enhancing neurite outgrowth in sensory neurons. Frozen storage does not affect activity, and 48 hours of conditioning is optimal. The addition of B-27 supplement enhances the regenerative effect of DPC secretome.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Review
Clinical Neurology
T. Marissal
Summary: Temporal lobe epilepsy is a severe neurological disease that affects up to 1% of adults, with roughly one third of patients being resistant to conventional pharmacological treatments. Surgical removal of the epileptic focus is often the last resort with no guarantee of symptom alleviation, highlighting the need for novel therapeutic approaches with limited side effects. Advances in understanding the cellular and molecular mechanisms of TLE are paving the way for new treatment perspectives.
REVUE NEUROLOGIQUE
(2021)
Article
Engineering, Biomedical
Flore Gouel, Kelly Timmerman, Philippe Gosset, Cedric Raoul, Mary Dutheil, Aurelie Jonneaux, Guillaume Garcon, Caroline Moreau, Veronique Danel-Brunaud, James Duce, Thierry Burnouf, Jean-Christophe Devedjian, David Devos
Summary: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with no cure. This study shows that heat-treated human platelet lysate may have neuroprotective effects in ALS models, suggesting it as a potential therapeutic approach.
Article
Neurosciences
Cylia Rochat, Nathalie Bernard-Marissal, Emma Kaellstig, Sylvain Pradervand, Florence E. Perrin, Patrick Aebischer, Cedric Raoul, Bernard L. Schneider
Summary: This study evaluated the therapeutic potential of gene therapy targeting mutated SOD1 in mature astrocytes. The results showed that this treatment gradually restored neuromuscular connections and significantly improved neuromuscular function. Gene therapy in the spinal cord protected the most vulnerable fast-fatigable motor neurons, and specific muscle fiber types were also preserved.
Article
Geriatrics & Gerontology
Laura Le Gall, William J. Duddy, Cecile Martinat, Virginie Mariot, Owen Connolly, Vanessa Milla, Ekene Anakor, Zamalou G. Ouandaogo, Stephanie Millecamps, Jeanne Laine, Udaya Geetha Vijayakumar, Susan Knoblach, Cedric Raoul, Olivier Lucas, Jean Philippe Loeffler, Peter Bede, Anthony Behin, Helene Blasco, Gaelle Bruneteau, Maria Del Mar Amador, David Devos, Alexandre Henriques, Adele Hesters, Lucette Lacomblez, Pascal Laforet, Timothee Langlet, Pascal Leblanc, Nadine Le Forestier, Thierry Maisonobe, Vincent Meininger, Laura Robelin, Francois Salachas, Tanya Stojkovic, Giorgia Querin, Julie Dumonceaux, Gillian Butler Browne, Jose-Luis Gonzalez De Aguilar, Stephanie Duguez, Pierre Francois Pradat
Summary: Muscle vesicles may be a potential source of vesicle-mediated toxicity in ALS, as they are shown to be toxic to MNs.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2022)
Article
Clinical Neurology
Lara El-Bazzal, Adeline Ghata, Clothilde Esteve, Jihane Gadacha, Patrice Quintana, Christel Castro, Nathalie Roeckel-Trevisiol, Frederique Lembo, Nicolas Lenfant, Andre Megarbane, Jean-Paul Borg, Nicolas Levy, Marc Bartoli, Yannick Poitelon, Pierre L. Roubertoux, Valerie Delague, Nathalie Bernard-Marissal
Summary: Charcot-Marie-Tooth (CMT) disease is a common inherited neurological disorder caused by mutations in over 100 genes. A study found that mutations in the FGD4 gene, which encodes FRABIN, can lead to aberrant myelination in the peripheral nervous system. The loss of FRABIN affects the NRG1/ERBB2/3 signaling pathway and impairs endocytic trafficking, contributing to myelination defects.
Article
Multidisciplinary Sciences
Marie Deck, Gerben Van Hameren, Graham Campbell, Nathalie Bernard-Marissal, Jerome Devaux, Jade Berthelot, Alise Lattard, Jean-Jacques Medard, Benoit Gautier, Sophie Guelfi, Scarlette Abbou, Patrice Quintana, Juan Manuel Chao de la Barca, Pascal Reynier, Guy Lenaers, Roman Chrast, Nicolas Tricaud
Summary: Lactate production through PKM2 enzyme and aerobic glycolysis is essential for the long-term maintenance of peripheral nerve axon physiology and function.
Article
Clinical Neurology
M. Khamaysa, M. Lefort, M. Pelegrini-Issac, A. Lackmy-Vallee, A. Preuilh, D. Devos, A. -S. Rolland, C. Desnuelle, M. Chupin, V. Marchand-Pauvert, G. Querin, Pierre-Francois Pradat
Summary: This study aimed to evaluate the predictive value of cervical spinal cord MRI parameters for motor capacity in ALS compared to clinical prognostic factors. Structural MRI measurements were significantly correlated with the ALSFRS-R score and its sub-scores. Multiple linear regression models combining spinal multimodal MRI and clinical factors could predict motor capacity in ALS.
JOURNAL OF NEUROLOGY
(2023)
Review
Neurosciences
Peter S. Spencer, Valerie S. Palmer, Glen E. Kisby, Emmeline Lagrange, B. Zane Horowitz, Raquel Valdes Angues, Jacques Reis, Jean-Paul Vernoux, Cedric Raoul, William Camu
Summary: The identity and role of environmental factors in sporadic amyotrophic lateral sclerosis (sALS) are not well understood, except for certain regions in the Western Pacific and French Alps. Exposure to DNA-damaging chemicals prior to the onset of motor neuron disease is strongly associated with ALS in these regions. This article discusses geographic clusters of ALS, familial cases, and young-onset cases in relation to their demographic and environmental associations, and highlights the importance of studying the lifetime exposome of young sALS cases for identifying ALS causation, mechanism, and prevention.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Richard Younes, Youssef Issa, Nadia Jdaa, Batoul Chouaib, Veronique Brugioti, Desire Challuau, Cedric Raoul, Frederique Scamps, Frederic Cuisinier, Cecile Hilaire
Summary: The secretome of DPSCs contains neurotrophic factors that promote motoneuron survival and provide neuroprotective benefits to the ALS mouse model. The mechanisms of action and specific factors involved need further investigation. GDF15 and HB-EGF protect SOD1(G93A) motoneurons against nitric oxide-induced death, suggesting their potential therapeutic role in ALS.
Review
Cell Biology
Rangariroyashe H. Chipika, Grainne Mulkerrin, Pierre-Francois Pradat, Aizuri Murad, Fabrice Ango, Cedric Raoul, Peter Bede
Summary: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive multi-system disease, characterized by degeneration of upper and lower motor neurons. However, there is increasing recognition of extra-motor pathology, including cerebellar pathology. Cerebellar degeneration in ALS is often overlooked, but it contributes to a variety of clinical symptoms and has widespread connectivity to spinal and supratentorial regions.
NEURAL REGENERATION RESEARCH
(2022)
Review
Cell Biology
Rangariroyashe H. Chipika, Grainne Mulkerrin, Pierre-Francois Pradat, Aizuri Murad, Fabrice Ango, Cedric Raoul, Peter Bede
Summary: Amyotrophic lateral sclerosis is a multi-system disease characterized by degeneration of upper and lower motor neurons. Recent studies have shown that cerebellar pathology also plays a role in the disease. However, most research has focused on supratentorial disease, and there is a lack of post-mortem validation. Clinical symptoms of amyotrophic lateral sclerosis, such as dysarthria, dysphagia, cognitive and behavioral deficits, saccade abnormalities, gait impairment, respiratory weakness and pseudobulbar affect may be exacerbated by co-existing cerebellar pathology.
NEURAL REGENERATION RESEARCH
(2022)
Review
Clinical Neurology
Philippe Gosset, William Camu, Cedric Raoul, Alexandre Mezghrani
Summary: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motoneurons in the brain and spinal cord. Disease onset is anatomically localized and progression occurs by spread to contiguous regions. This review discusses the relevance of prion-like propagation as a pathogenic determinant in disease progression.
BRAIN COMMUNICATIONS
(2022)
Article
Neurosciences
Nihal A. Salem, Lawrence Manzano, Michael W. Keist, Olga Ponomareva, Amanda J. Roberts, Marisa Roberto, R. Dayne Mayfield
Summary: This study identified cell-type specific gene expression changes associated with alcohol dependence in the medial prefrontal cortex of mice. The results revealed dysregulated gene co-expression networks and differentially expressed genes in multiple cell types, highlighting the involvement of inhibitory neurons and astrocytes in alcohol dependence. Novel targets for studying molecular mechanisms contributing to alcohol dependence were also identified.
NEUROBIOLOGY OF DISEASE
(2024)
Article
Neurosciences
Laura E. Hawley, Megan Stringer, Abigail J. Deal, Andrew Folz, Charles R. Goodlett, Randall J. Roper
Summary: This study found that the overexpression of DYRK1A protein in Down syndrome mice varies with age, sex, and brain region, and reducing the copy number of Dyrk1a can decrease the expression of DYRK1A. These sex-specific patterns of DYRK1A overexpression may provide mechanistic targets for therapeutic intervention in Down syndrome.
NEUROBIOLOGY OF DISEASE
(2024)