Article
Neurosciences
Albert J. B. Lee, Tyler E. E. Kittel, Renaid B. B. Kim, Thao-Nguyen Bach, Tian Zhang, Cassie S. S. Mitchell
Summary: The study aimed to determine the most beneficial pathophysiological treatment targets for ALS. The results showed that treatments targeting inflammation were best at delaying disease onset, oxidative stress treatments significantly prolonged survival, and excitability treatments improved overall health status. The best pathophysiological treatment category varied with disease progression and combination treatments targeting multiple categories performed better than monotherapies at end-stage.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Pharmacology & Pharmacy
Silvia Scaricamazza, Illari Salvatori, Susanna Amadio, Valentina Nesci, Alessio Torcinaro, Giacomo Giacovazzo, Aniello Primiano, Michela Gloriani, Niccolo Candelise, Luisa Pieroni, Jean-Philippe Loeffler, Frederique Rene, Cyril Quessada, Tesfaye W. Tefera, Hao Wang, Frederik J. Steyn, Shyuan T. Ngo, Gabriella Dobrowolny, Elisa Lepore, Andrea Urbani, Antonio Musaro, Cinzia Volonte, Elisabetta Ferraro, Roberto Coccurello, Cristiana Valle, Alberto Ferri
Summary: The therapeutic potential of the multi-target drug trimetazidine was evaluated in SOD1(G93A) mice. The results showed that trimetazidine delayed disease progression, improved motor function and metabolism, and increased overall survival of the mice.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Nuria Gaja-Capdevila, Neus Hernandez, Xavier Navarro, Mireia Herrando-Grabulosa
Summary: The study demonstrated that Sig-1R ligands, including three different drugs, can partially alleviate muscle function impairment in ALS patients and increase the number of surviving motor neurons. Furthermore, these drugs showed varying effects in improving muscle function and protecting neuromuscular junctions. Although more research is needed to determine their exact mechanisms of action, Sig-1R ligands have the potential to be promising tools for ALS treatment.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Neurosciences
Xiaojiao Xu, Jingjing Zhang, Song Li, Murad Al-Nusaif, Qinming Zhou, Sheng Chen, Weidong Le
Summary: The study found that neuroinflammation in the early pathogenesis of ALS is associated with increased immune-related genes, and BST2 may serve as a potential target for ameliorating microglia-mediated neuroinflammation pathologies in ALS.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Medicine, General & Internal
Wen-Chao Liu, Na Liu, Yan Wang, Chen Huang, Yan-Fang Li, Hao Wang, Xiao-Gang Li, Min Deng
Summary: Research shows that motor neurons (MNs) derived from ALS patient-specific iPSC lines can replicate key aspects of ALS pathogenesis, providing insights into the disease's pathophysiological processes. Incremental mutant expressions of SOD1 in MNs may disrupt cellular function, leading to intracellular calcium disturbances and contributing to the onset of the disease.
CHINESE MEDICAL JOURNAL
(2021)
Article
Neurosciences
Lei Zhu, Fan Hu, Cheng Li, Caixiang Zhang, Ruiwen Hang, Renshi Xu
Summary: The study found that during the progression of ALS, the distribution and expression of PLIN 4 changed, potentially contributing to neural cell death by modulating lipid metabolism and neural cell proliferation.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Neurosciences
Isabella Orienti, Monica Armida, Gabriella Dobrowolny, Rita Pepponi, Gabriella Sollazzini, Antonella Pezzola, Irene Casola, Antonio Musaro, Patrizia Popoli, Rosa Luisa Potenza
Summary: Fenretinide (FEN) shows potential in preventing and overcoming the toxicity of mutant SOD1 (mSOD1) in amyotrophic lateral sclerosis (ALS). Administration of a new nanomicellar fenretinide formulation (NanoMFen) can ameliorate disease progression in ALS, with its efficacy influenced by gender and showing better effects in female subjects.
Article
Pharmacology & Pharmacy
Yujun Zhou, Jingshu Tang, Jiaqi Lan, Yong Zhang, Hongyue Wang, Qiuyu Chen, Yuying Kang, Yang Sun, Xinhong Feng, Lei Wu, Hongtao Jin, Shizhong Chen, Ying Peng
Summary: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with unmet medical needs. Honokiol (HNK) has therapeutic effects in other neurologic disease models and also showed protection in ALS disease models. Mechanistic studies revealed that HNK alleviated oxidative stress and improved mitochondrial function in ALS cells.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Neurosciences
Cassandra N. Dennys, Florence Roussel, Rochelle Rodrigo, Xiaojin Zhang, Andrea Sierra Delgado, Annalisa Hartlaub, Asya Saelim-Ector, Will Ray, Sarah Heintzman, Ashley Fox, Stephen J. Kolb, Joseph Beckman, Maria Clara Franco, Kathrin Meyer
Summary: Patient diversity and unknown disease cause pose challenges for drug development and clinical trial design in ALS. Reprogramming patient fibroblasts to neuronal progenitor cells can generate disease relevant cell types for compound testing. CuATSM, currently in clinical trial for ALS, showed a differential effect on neuronal survival in co-culture assays. Elevated mitochondrial respiration was observed in all CuATSM-responders, suggesting a potential metabolic mechanism for CuATSM's therapeutic effects.
Article
Biochemistry & Molecular Biology
Natalia Nowicka, Kamila Szymanska, Judyta Juranek, Kamila Zglejc-Waszak, Agnieszka Korytko, Michal Zalecki, Malgorzata Chmielewska-Krzesinska, Krzysztof Wasowicz, Joanna Wojtkiewicz
Summary: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unclear pathogenesis. RAGE and its ligands have been found to play an important role in the pathogenesis of ALS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Federica Rey, Stefania Marcuzzo, Silvia Bonanno, Matteo Bordoni, Toniella Giallongo, Claudia Malacarne, Cristina Cereda, Gian Vincenzo Zuccotti, Stephana Carelli
Summary: Study shows RNA metabolism plays a key role in ALS pathogenesis, with long non-coding RNAs implicated in the development of ALS. Analysis of a panel of lncRNAs reveals specific dysregulation in early stages of ALS, suggesting lncRNAs could potentially serve as novel disease modifiers or biomarkers.
Article
Geriatrics & Gerontology
Suzanna Edgar, Melina Ellis, Nur Adilah Abdul-Aziz, Khean-Jin Goh, Nortina Shahrizaila, Marina L. Kennerson, Azlina Ahmad-Annuar
Summary: This study identified mutations in SOD1 and C9orf72 genes in a multi-ethnic Malaysian ALS cohort, with a mutation frequency of 5.9%. No mutations were found in FUS and TARDBP genes. Further investigation is needed to uncover novel genes and disease pathways in ALS.
NEUROBIOLOGY OF AGING
(2021)
Article
Cell Biology
Veronica Granatiero, Nicole M. Sayles, Angela M. Savino, Csaba Konrad, Michael G. Kharas, Hibiki Kawamata, Giovanni Manfredi
Summary: ALS is a complex disease involving motor neuron degeneration, with emerging evidence suggesting the importance of astrocytes and the MTOR pathway in disease pathogenesis. Modulation of the astrocytic IGF1R-MTOR pathway may present a potential therapeutic strategy for SOD1 ALS and other neurological disorders.
Review
Clinical Neurology
Philippe Corcia, Christian Lunetta, Patrick Vourc'h, Pierre-Francois Pradat, Helene Blasco
Summary: This article reviews the progress in the diagnosis, monitoring, and treatment of amyotrophic lateral sclerosis (ALS). Despite the difficulty in diagnosing and the lack of a cure for ALS, there is evidence to suggest that an optimistic view of ALS management in the coming years is now realistic.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Biochemical Research Methods
Lin Chen, Ningyuan Wang, Yingzhen Zhang, Dongxiao Li, Caili He, Zhongzhong Li, Jian Zhang, Yansu Guo
Summary: This study analyzed the differentially expressed proteins (DEPs) in the spinal cord of ALS mice at the onset stage. The findings suggest that immunity and inflammation play a crucial role in the early development of ALS. Additionally, potential biomarkers were identified, providing new insights into the pathological mechanisms of ALS.
JOURNAL OF PROTEOMICS
(2023)
Review
Biochemistry & Molecular Biology
T. P. Nhung Nguyen, Mandeep Kumar, Ernesto Fedele, Giambattista Bonanno, Tiziana Bonifacino
Summary: This study provides an overview of the important role of miRNAs in neurodegenerative diseases. It shows that miRNAs are dysregulated in these diseases and may serve as potential biomarkers for diagnosis and prognosis. The study also summarizes the applications of miRNA-based therapies, including inhibiting or promoting miRNA expression. The researchers identify common miRNA signatures associated with various diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Davide Marangon, Matteo Audano, Silvia Pedretti, Marta Fumagalli, Nico Mitro, Davide Lecca, Donatella Caruso, Maria P. Abbracchio
Summary: This study investigates the role of physiological GPR17 downregulation in oligodendrocyte (OL) metabolism through transcriptomics, metabolomics, and lipidomics analysis. The results show that silencing GPR17 leads to an increase in mature OL markers and alteration of genes related to glucose metabolism and lipid biosynthesis. Additionally, an increased lactate release contributes to the enhanced OL maturation caused by GPR17 downregulation. The study also reveals changes in the kinetics of specific myelin lipid classes due to GPR17 depletion.
Article
Cell Biology
Tiziana Bonifacino, Laura Micheli, Carola Torazza, Carla Ghelardini, Carlo Farina, Giambattista Bonanno, Marco Milanese, Lorenzo Di Cesare Mannelli, Michael W. Scherz
Summary: Dimiracetam more potently inhibits NMDA-induced [H-3]D-aspartate release in vitro and shows superior efficacy in a model of painful osteoarthritis after oral administration compared to its isolated enantiomers. Additionally, the non-racemic mixture MP-101 has even greater potency than dimiracetam and exhibits improved anti-neuropathic effects in a chronic pain model.
Article
Cell Biology
Francesca Provenzano, Sophie Nyberg, Debora Giunti, Carola Torazza, Benedetta Parodi, Tiziana Bonifacino, Cesare Usai, Nicole Kerlero de Rosbo, Marco Milanese, Antonio Uccelli, Pamela J. Shaw, Laura Ferraiuolo, Giambattista Bonanno
Summary: This study found that extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) can reduce the toxic phenotype and neurotoxicity of astrocytes in amyotrophic lateral sclerosis (ALS), suggesting a potential therapeutic strategy.
Article
Biochemistry & Molecular Biology
Lia Forti, Elona Ndoj, Jessica Mingardi, Emanuele Secchi, Tiziana Bonifacino, Emanuele Schiavon, Giulia Carini, Luca La Via, Isabella Russo, Marco Milanese, Massimo Gennarelli, Giambattista Bonanno, Maurizio Popoli, Alessandro Barbon, Laura Musazzi
Summary: Traumatic stress is a significant risk factor for psychiatric disorders. This study investigates the effects of acute footshock stress and ketamine on the glutamatergic synaptic plasticity in the prefrontal cortex. The findings suggest that acute stress and ketamine induce changes in dopamine-dependent long-term potentiation (LTP) as well as ionotropic glutamate receptor subunit expression and localization. Further research is needed, but this initial report supports the potential benefit of acute ketamine in mitigating the impact of acute traumatic stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Matilde Balbi, Giambattista Bonanno, Tiziana Bonifacino, Marco Milanese
Summary: Microglia cells are immune cells in the central nervous system that play a role in neuroinflammation. Their activation can have both beneficial and harmful effects due to the release of different molecules. Group I metabotropic glutamate receptors (mGluRs) are molecular structures that may impact the phenotype of microglia cells, and their role in specific conditions, including amyotrophic lateral sclerosis (ALS), is explored in this review.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Marta Boccazzi, Stefano Raffaele, Thomas Zanettin, Maria P. Abbracchio, Marta Fumagalli
Summary: Neurodevelopmental disorders (NDDs) encompass a range of congenital pathological conditions that affect cognitive, social behavior, and sensory/motor functioning. Recent research has linked genetic disorders involving purine metabolism to autism-like behaviors in humans. Dysregulated purine and pyrimidine levels have also been found in biofluids of individuals with other NDDs. Blocking specific purinergic pathways has been shown to reverse cognitive and behavioral defects in rodent models of NDDs. These findings suggest that targeting P2 receptor signaling could lead to the development of more specific treatments and early detection markers for NDDs.
Article
Biology
Minna Christiansen Lund, Ditte Gry Ellman, Pernille Vinther Nielsen, Stefano Raffaele, Marta Fumagalli, Raphael Guzman, Matilda Degn, Roberta Brambilla, Morten Meyer, Bettina Hjelm Clausen, Kate Lykke Lambertsen
Summary: Selective inhibition of solTNF can alleviate the inflammatory response, alter microglial responses, increase myelin preservation, and improve functional outcomes in spinal cord injury (SCI). This finding suggests that targeting solTNF holds therapeutic potential for SCI.
Article
Biochemistry & Molecular Biology
Jessica Mingardi, Elona Ndoj, Tiziana Bonifacino, Paulina Misztak, Matteo Bertoli, Luca La Via, Carola Torazza, Isabella Russo, Marco Milanese, Giambattista Bonanno, Maurizio Popoli, Alessandro Barbon, Laura Musazzi
Summary: Stress is a major risk factor for neuropsychiatric disorders, including major depressive disorder. Using a rat model of depression, researchers found that chronic stress induced morphological, functional, and molecular changes in the hippocampus, which were reversed by acute subanesthetic ketamine. In this study, they focused on the medial prefrontal cortex (mPFC) and found that most changes induced by stress were observed in vulnerable animals and rescued by ketamine, while others were only found in resilient animals or induced by ketamine treatment. Importantly, these changes were specific to the mPFC and not previously demonstrated in the hippocampus. Overall, the results suggest that acute antidepressant ketamine can reverse stress-induced glutamatergic changes in a brain-area-specific manner.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Carola Torazza, Francesca Provenzano, Elena Gallia, Maria Cerminara, Matilde Balbi, Tiziana Bonifacino, Sara Tessitore, Silvia Ravera, Cesare Usai, Ilaria Musante, Aldamaria Puliti, Ludo Van Den Bosch, Paymaan Jafar-nejad, Frank Rigo, Marco Milanese, Giambattista Bonanno
Summary: This study demonstrates that downregulating mGluR5 expression can alleviate the reactive response and neurotoxicity of SOD1(G93A) astrocytes towards motor neurons, suggesting that mGluR5 may be a promising therapeutic target in ALS.