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
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)
Review
Biochemistry & Molecular Biology
Katarina Maksimovic, Mohieldin Youssef, Justin You, Hoon-Ki Sung, Jeehye Park
Summary: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons, leading to muscle weakness, paralysis, and eventual death. Recent research has shown that ALS is not only limited to motor neurons, but also involves systemic metabolic dysfunction. This review examines the metabolic dysfunction in ALS at various levels, including muscle tissue, adipose tissue, liver, pancreas, and the central nervous system. It also discusses the future prospects of metabolic research in ALS and potential treatment options.
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
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
Clinical Neurology
Ji He, Jiayu Fu, Wei Zhao, Chuan Ren, Ping Liu, Lu Chen, Dan Li, Lu Tang, Lequn Zhou, Yixuan Zhang, Xinran Ma, Gaoqi Zhang, Nan Li, Dongsheng Fan
Summary: This study found a significant increase in the prevalence and degree of hypermetabolism in ALS patients compared to matched controls in China. The metabolic index was closely associated with disease progression and body composition, serving as an independent prognostic indicator for worse survival in ALS.
JOURNAL OF NEUROLOGY
(2022)
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
Biochemistry & Molecular Biology
Di Wen, Yingxiao Ji, Yuanyuan Li, Weisong Duan, Yanyan Wang, Zhongyao Li, Meichun Tao, Yakun Liu
Summary: The study suggests that OPTN gene therapy could be an effective strategy to increase autophagy and protect mitochondria, thereby preventing the progression of ALS.
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
Biochemistry & Molecular Biology
Katharina Wintz, Julia Post, Karl-Josef Langen, Dieter Willbold, Antje Willuweit, Janine Kutzsche
Summary: Amyotrophic lateral sclerosis (ALS) is a deadly disease with no cure, causing complete muscle loss and respiratory arrest. Only three symptomatic drugs have been approved by the FDA so far. RD2RD2, a new drug candidate, has shown the ability to delay symptom onset in mouse models of ALS.
Article
Clinical Neurology
Sebastian Michels, Deborah Kurz, Angela Rosenbohm, Raphael S. Peter, Steffen Just, Hansjörg Baezner, Axel Boertlein, Christian Dettmers, Hans-Jürgen Gold, Andreas Kohler, Markus Naumann, Peter Ratzka, Albert C. Ludolph, Dietrich Rothenbacher, Gabriele Nagel, Johannes Dorst
Summary: This large-scale population-based case-control study examined the associations between blood lipid levels and the onset and prognosis of ALS. The results showed a positive correlation between high total cholesterol levels and the risk of ALS. Furthermore, higher levels of HDL and LDL cholesterol were associated with higher mortality in ALS patients, whereas higher triglyceride levels were associated with lower mortality.
JOURNAL OF NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Julia Post, Anja Schaffrath, Ian Gering, Sonja Hartwig, Stefan Lehr, N. Jon Shah, Karl-Josef Langen, Dieter Willbold, Janine Kutzsche, Antje Willuweit
Summary: The study demonstrates that RD2RD2 has therapeutic potential in SOD1(G93A) mice, significantly improving performance in behavioral and motor coordination tests and slowing the progression of neurodegenerative phenotype. Additionally, treatment of SOD1(G93A) mice leads to a significant reduction in glial cell activation and rescue of neurons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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)
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
Clinical Neurology
Angela Gento-Caro, Esther Vilches-Herrando, Victoria Garcia-Morales, Federico Portillo, Guillermo Rodriguez-Bey, David Gonzalez-Forero, Bernardo Moreno-Lopez
Summary: This study uncovered the important role of LPA-LPA(1) signaling in the degeneration of MN in ALS mice. Inhibiting LPA(1) can slow down disease progression, highlighting it as a potential target and/or biomarker in ALS.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Article
Clinical Neurology
Jeryn Chang, Thomas B. Shaw, Cory J. Holdom, Pamela A. McCombe, Robert D. Henderson, Jurgen Fripp, Markus Barth, Christine C. Guo, Shyuan T. Ngo, Frederik J. Steyn
Summary: This study found that lower hypothalamic volume is associated with lower and higher BMI in ALS patients, unlike AD patients and controls. Hypothalamic volume is not related to loss of appetite or hypermetabolism. In ALS patients, lower hypothalamic volume with lower BMI is associated with weight loss and earlier death.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Cory J. Holdom, Jordi W. J. van Unnik, Ruben P. A. van Eijk, Leonard H. van den Berg, Robert D. Henderson, Shyuan T. Ngo, Frederik J. Steyn
Summary: This study examined the use of wrist and hip accelerometers to measure activity levels in patients with Motor Neuron Disease (MND) compared to controls. The results showed that wrist-based measurements were more variable and had differing sensitivity to specific functional outcomes compared to hip-based measurements. Careful selection of measurement devices and analysis methods is necessary for at-home monitoring of disease progression in patients with MND.
JOURNAL OF NEUROLOGY
(2023)
Review
Clinical Neurology
Jeremy M. Shefner, Antonio Musaro, Shyuan T. Ngo, Christian Lunetta, Frederik J. Steyn, Richard Robitaille, Mamede De Carvalho, Seward Rutkove, Albert C. Ludolph, Luc Dupuis
Summary: Amyotrophic lateral sclerosis (ALS), a major motor neuron disease, has long been considered as primarily affecting motor neurons and neuromuscular junctions, with muscle changes being secondary. However, recent studies have shown that skeletal muscle dysfunction might contribute to muscle weakness, as well as the degeneration of neuromuscular junctions and motor neurons in ALS. This article explores the various potential roles of skeletal muscle in ALS pathophysiology and compares ALS to other motor neuron diseases, providing insights for future research and treatment.
Editorial Material
Biochemistry & Molecular Biology
Sara Marinelli, Roberto Coccurello
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Valeria Taliani, Giulia Buonaiuto, Fabio Desideri, Adriano Setti, Tiziana Santini, Silvia Galfre, Leonardo Schirone, Davide Mariani, Giacomo Frati, Valentina Valenti, Sebastiano Sciarretta, Emerald Perlas, Carmine Nicoletti, Antonio Musaro, Monica Ballarino
Summary: Long noncoding RNAs (lncRNAs) play a critical role in heart physiology and disease. We identified a lncRNA called pCharme that is associated with chromatin and is involved in myogenesis and cardiac muscle remodeling in mice. Through various molecular analyses, we found that pCharme is specifically expressed in cardiomyocytes and is important for their maturation and cardiac development. The loss of pCharme leads to delayed cardiomyocyte maturation and morphological alterations in the ventricular myocardium. This study provides valuable insights into a novel lncRNA-mediated regulatory mechanism in heart development and has implications for future theranostic applications targeting the Charme locus.
Review
Neurosciences
Matthias Schmitz, Niccolo Candelise, Sezgi Canaslan, Hermann C. Altmeppen, Jakob Matschke, Markus Glatzel, Neelam Younas, Saima Zafar, Peter Hermann, Inga Zerr
Summary: Alpha-synucleinopathies, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, are neurodegenerative diseases characterized by intracellular inclusions of misfolded alpha-synuclein. The pathological overlap between Parkinson's disease and dementia with Lewy bodies raises the question of whether they are the same or different diseases. Protein seeding assays, such as real-time quaking-induced conversion, can help distinguish between different types of alpha-synucleinopathies by analyzing the conversion properties of misfolded alpha-synuclein. Understanding the influence of different conformers of misfolded alpha-synuclein on disease progression and phenotype will be crucial for personalized medical treatment in the future.
TRANSLATIONAL NEURODEGENERATION
(2023)
Review
Cell Biology
Niccolo Candelise, Francesca Santilli, Jessica Fabrizi, Daniela Caissutti, Zaira Spinello, Camilla Moliterni, Loreto Lancia, Simona Delle Monache, Vincenzo Mattei, Roberta Misasi
Summary: Despite the lack of available therapies for neurodegenerative disorders, cell therapy using stem cells from various sources, such as dental pulp stem cells, has shown promise in preclinical models. These stem cells can be reprogrammed for neural differentiation and have potential applications in the treatment of nervous system disorders. This review summarizes the advancements and differences in the maintenance, differentiation, and potential clinical application of such stem cells.
Editorial Material
Biochemistry & Molecular Biology
Sara Marinelli, Roberto Coccurello
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Niccolo Candelise, Daniela Caissutti, Henri Zenuni, Valentina Nesci, Silvia Scaricamazza, Illari Salvatori, Zaira Spinello, Vincenzo Mattei, Tina Garofalo, Alberto Ferri, Cristiana Valle, Roberta Misasi
Summary: TDP43 is a nuclear protein associated with ALS, and its cytoplasmic inclusions are characteristic of the disease. Acute stress triggers the mobilization and aggregation of TDP43 in the cytoplasm through different pathways. By using solubility assays, thioflavin-based microscopy, and flow cytometry, we were able to detect the formation of a 25 kDa C-terminal fragment of TDP43 in vitro for the first time, which is a pathological hallmark of ALS. Our findings suggest that chronic stress better recapitulates the cell biology of TDP43 proteinopathies compared to acute stress, and that TDP43 may form amyloids as a stress response.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Clinical Neurology
Albert Ludolph, Luc Dupuis, Edward Kasarskis, Frederik Steyn, Shyuan Ngo, Christopher McDermott
Summary: Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease with non-motor symptoms. Nutritional status and metabolic balance have been found to contribute to faster disease progression and earlier death. Cellular changes, including mitochondrial dysfunction, are also shown to contribute to bioenergetic failure in ALS. Modifying energy balance in ALS shows potential as a treatment option and multiple clinical trials are underway.
NATURE REVIEWS NEUROLOGY
(2023)
Article
Cell & Tissue Engineering
Timothy J. Tracey, Leanne Jiang, Melinder K. Gill, Samara N. Ranie, Dmitry A. Ovchinnikov, Ernst J. Wolvetang, Shyuan T. Ngo
Summary: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, and the TDP-43 protein plays a crucial role in its pathophysiology. This study used the CRISPR-Cas9 system to introduce a heterozygous missense mutation (c.1144G > A, p.A382T) in exon 6 of the TARDBP gene into iPSCs derived from a healthy individual. The edited iPSCs maintained normal cellular morphology, pluripotency markers expression, tri-lineage differentiation ability, and karyotype.
STEM CELL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Riccardo Turchi, Francesca Sciarretta, Veronica Ceci, Marta Tiberi, Matteo Audano, Silvia Pedretti, Concetta Panebianco, Veronica Nesci, Valerio Pazienza, Alberto Ferri, Simone Carotti, Valerio Chiurchiu, Nico Mitro, Daniele Lettieri-Barbato, Katia Aquilano
Summary: Friedreich's ataxia (FA) is a neurodegenerative disease caused by a mutation in the FXN gene, leading to deficiency of mitochondrial frataxin. This study investigated the role of visceral white adipose tissue (vWAT) in FA-related metabolic complications. The findings suggest that vWAT abnormalities contribute to metabolic issues in FA, and a butyrate-enriched diet may be a safe and promising adjunct for FA management.
Review
Biochemistry & Molecular Biology
Debora Cutuli, Davide Decandia, Giacomo Giacovazzo, Roberto Coccurello
Summary: Physical exercise has beneficial effects on gut microbiota composition and functionality, potentially alleviating the pathophysiology of Alzheimer's disease through the gut-brain axis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
