Article
Behavioral Sciences
Agueda Ferrer-Donato, Ana Contreras, Paloma Fernandez, Carmen M. Fernandez-Martos
Summary: The study found that leptin treatment in the ALS mouse model altered expression of adipokines and metabolic proteins, reduced weight loss decline, prolonged disease duration, and improved motor performance. This suggests that leptin could be a potential novel treatment approach for ALS.
BRAIN AND BEHAVIOR
(2022)
Article
Clinical Neurology
Aydan Kahriman, James Bouley, Idil Tuncali, Elif O. Dogan, Mariana Pereira, Thuyvan Luu, Daryl A. Bosco, Samer Jaber, Owen M. Peters, Robert H. Brown Jr, Nils Henninger
Summary: Repetitive traumatic brain injury may increase the risk of FTD/ALS-associated pathology and behavioral deficits in mice with C9orf72 hexanucleotide repeat expansion.
Article
Biochemistry & Molecular Biology
Braulio Valdebenito-Maturana, Matias Ignacio Rojas-Tapia, Monica Carrasco, Juan Carlos Tapia
Summary: This study found that mutations in TAR DNA binding protein 43 (TDP-43) are associated with the occurrence and progression of amyotrophic lateral sclerosis (ALS). The results showed that TDP-43(M337V) mutation induced global changes in gene expression and transposable elements (TEs) levels, and many genetic pathways overlapped with TEs activity, suggesting that TEs control the expression of several key genes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Santiago E. Charif, M. Florencia Vassallu, Lara Salvanal, Lionel M. Igaz
Summary: Protein synthesis is crucial for cell metabolism, and protein imbalances can cause neurodegenerative diseases. Neurons are particularly susceptible to the harmful effects of protein overload, and with age, proteostatic mechanisms become less effective. Research on therapeutic compounds aimed at restoring protein balance is of great importance.
NEURAL REGENERATION RESEARCH
(2022)
Article
Neurosciences
Xuebing Ding, Zhi Xiang, Chi Qin, Yongkang Chen, Haiyan Tian, Lin Meng, Danhao Xia, Han Liu, Jia Song, Jun Fu, Mingming Ma, Xuejing Wang
Summary: The research findings suggest that the transmission of pathological TDP-43 along the pyramidal tract induces ALS-like neuropathology and symptoms. This provides direct evidence for the potential mechanism of TDP-43 proteinopathy.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Agueda Ferrer-Donato, Ana Contreras, Laura M. Frago, Julie A. Chowen, Carmen M. Fernandez-Martos
Summary: The study revealed alterations in leptin signaling in the spinal cord and hypothalamus of TDP-43-induced mice, offering new evidence about the pathways linking leptin signaling to ALS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Poulomi Banerjee, Elizabeth Elliott, Olivia M. Rifai, Judi O'Shaughnessy, Karina McDade, Sharon Abrahams, Siddharthan Chandran, Colin Smith, Jenna M. Gregory
Summary: This article explores the molecular mechanisms underlying cognitive dysfunction in patients with amyotrophic lateral sclerosis. It identifies significantly dysregulated genes between cognitively affected and unaffected brain regions, as well as macromolecular complex regulation associated with cognitive resilience.
JOURNAL OF PATHOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Greta Grassmann, Mattia Miotto, Lorenzo Di Rienzo, Federico Salaris, Beatrice Silvestri, Elsa Zacco, Alessandro Rosa, Gian Gaetano Tartaglia, Giancarlo Ruocco, Edoardo Milanetti
Summary: This article investigates the protein aggregation process in ALS, providing a computational model of interaction based on the evaluation of shape complementarity at the molecular interfaces. The study proposes and assesses possible association mechanisms between CTFs, and performs molecular docking and additional MD simulations to propose possible complexes and evaluate their stability, focusing on high shape complementarity and involvement of beta 3 and beta 5 strands at the interfaces.
Article
Neurosciences
Haoyun Zhang, Hao Li, Bingkun Huang, Shaoye Wang, Ying Gao, Fandi Meng, Yanchun Chen, Fenghua Zhou, Yingjun Guan, Xin Wang
Summary: The study found early activation of the canonical NLRP3 inflammasome induced pyroptosis in ventral horn neurons in ALS mice, which may participate in motor neuron degeneration and initiate neuroinflammatory processes during ALS progression.
Review
Biochemistry & Molecular Biology
T. G. Sahana, Ke Zhang
Summary: Amyotrophic lateral sclerosis is a fatal motor neuron degenerative disease with multiple genetic and non-genetic risk factors. Cellular stress plays a significant role in ALS conditions, with the MAPK pathway being implicated in the disease pathogenesis and potential drug targeting.
Article
Immunology
Hazel Quek, Carla Cuni-Lopez, Romal Stewart, Tiziana Colletti, Antonietta Notaro, Tam Hong Nguyen, Yifan Sun, Christine C. Guo, Michelle K. Lupton, Tara L. Roberts, Yi Chieh Lim, Lotta E. Oikari, Vincenzo La Bella, Anthony R. White
Summary: Researchers successfully recapitulated the pathological features of ALS using monocyte-derived microglia-like cells, and found significant cellular functional differences in ALS patients with different disease progression rates. These findings help to reveal patient heterogeneity in ALS and provide a basis for personalized treatment.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Integrative & Complementary Medicine
Eun Jin Yang
Summary: The combined treatment of Bojungikgi-tang and riluzole may have anti-inflammatory effects and regulate autophagy dysfunction in TDP-43-induced ALS.
CHINESE JOURNAL OF INTEGRATIVE MEDICINE
(2023)
Article
Neurosciences
Kyle J. Trageser, Eun-Jeong Yang, Chad Smith, Ruth Iban-Arias, Tatsunori Oguchi, Maria Sebastian-Valverde, Umar Haris Iqbal, Henry Wu, Molly Estill, Md Al Rahim, Urdhva Raval, Francis J. Herman, Yong Jie Zhang, Leonard Petrucelli, Giulio Maria Pasinetti
Summary: Hexanucleotide repeat expansions in C9orf72 gene cause frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) and lead to the production of toxic dipeptide repeat (DPR) proteins, with poly(glycine-arginine) (GR) being the most toxic and accumulating in relevant brain regions. Neuroinflammation is a driving factor in the disease, and increased inflammasome-mediated neuroinflammation is observed in C9orf72 FTD/ALS mice, suggesting a role for HRE in innate immunity and the NLRP3 inflammasome as a potential therapeutic target.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Microbiology
Yichen Li, Xutao Lin, Wenxia Wang, Wenyu Wang, Sijing Cheng, Yibo Huang, Yifeng Zou, Jia Ke, Lixin Zhu
Summary: GBP5 plays an important role in the pathogenesis of inflammatory bowel diseases (IBD) by regulating the expression of proinflammatory cytokines and chemokines in intestinal immune cells. Targeting GBP5 could be an effective strategy for the management of IBD.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Cell Biology
Shi-Shi Jiang, Meng-Ni Gong, Wei Rao, Wen Chai, Wen-Zhi Chen, Xiong Zhang, Hong-Bing Nie, Ren-Shi Xu
Summary: This study found that the pathogenesis of amyotrophic lateral sclerosis (ALS) is closely linked to a deficiency in 5-hydroxytryptamine (5-HT). By administering 5-HT receptor antagonists to ALS mouse models, the researchers discovered that these antagonists affected the expression and distribution of TAR DNA binding protein 43 (TDP-43) and superoxide dismutase 1 G93A (SOD1-G93A), as well as activated glial cells. The study suggests that targeting 5-HT could be a potential therapeutic approach for ALS.
NEURAL REGENERATION RESEARCH
(2023)
Article
Clinical Neurology
Wenting Guo, Haibo Wang, Arun Kumar Tharkeshwar, Julien Couthouis, Elke Braems, Pegah Masrori, Evelien Van Schoor, Yannan Fan, Karan Ahuja, Matthieu Moisse, Maarten Jacquemyn, Rodrigo Furtado Madeiro da Costa, Madhavsai Gajjar, Sriram Balusu, Tine Tricot, Laura Fumagalli, Nicole Hersmus, Rekin's Janky, Francis Impens, Pieter Vanden Berghe, Ritchie Ho, Dietmar Rudolf Thal, Rik Vandenberghe, Muralidhar L. Hegde, Siddharthan Chandran, Bart De Strooper, Dirk Daelemans, Philip Van Damme, Ludo Van den Bosch, Catherine Verfaillie
Summary: In this study, we identified NEK6 as a novel therapeutic target for C9orf72 FTD/ALS by performing a kinome-wide CRISPR/Cas9 knock-out screen in human induced pluripotent stem cell-derived cortical neurons. NEK6 was found to regulate poly(PR)-mediated p53-related DNA damage.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Jolien Schaeverbeke, Sandra O. Tome, Alicja Ronisz, Simona Ospitalieri, Christine A. F. von Arnim, Markus Otto, Rik Vandenberghe, Dietmar Rudolf Thal
Summary: This study quantitatively assessed neuronal density and pathology in the nucleus basalis of Meynert (nbM) of 47 cases, including different variants of primary progressive aphasia (PPA) and Alzheimer's disease (AD). The results showed that reduced nbM neuronal density was only found in AD. PPA patients with underlying AD pathology exhibited lower neuronal densities, while those with frontotemporal lobar degeneration (FTLD) were unaffected.
ALZHEIMERS & DEMENTIA
(2023)
Review
Clinical Neurology
Sean W. Willemse, Peter Harley, Ruben P. A. van Eijk, Koen C. Demaegd, Pavol Zelina, R. Jeroen Pasterkamp, Philip van Damme, Caroline Ingre, Wouter van Rheenen, Jan H. Veldink, Matthew C. Kiernan, Ammar Al-Chalabi, Leonard H. van den Berg, Pietro Fratta, Michael A. van Es
Summary: Amyotrophic lateral sclerosis (ALS) is a deadly neurodegenerative disease with limited treatment options. A specific gene polymorphism in the UNC13A gene has been found to increase the risk of ALS and frontotemporal dementia (FTD), and can modify the disease phenotype in ALS patients. UNC13A is involved in maintaining synaptic active zones and its depletion leads to impaired neurotransmission. Recent discoveries have identified UNC13A as a potential therapeutic target, with ongoing trials using lithium carbonate and considering antisense oligonucleotides. Knowledge of UNC13A's distinct phenotype is important for future clinical trials.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Neurosciences
Katarina Stoklund Dittlau, Lisanne Terrie, Pieter Baatsen, Axelle Kerstens, Lim De Swert, Rekin's Janky, Nikky Corthout, Pegah Masrori, Philip Van Damme, Poul Hyttel, Morten Meyer, Lieven Thorrez, Kristine Freude, Ludo van den Bosch
Summary: In this study, the researchers investigated the role of astrocytes in amyotrophic lateral sclerosis (ALS) using a human motor unit microfluidics model. They found that astrocyte homeostasis was dysregulated in ALS patients, leading to increased inflammation. Additionally, co-culture with ALS astrocytes resulted in cytotoxic effects on motor neuron-neurite outgrowth and neuromuscular junction functionality, which were partially or fully rescued by control astrocytes. The study highlights the complex role of astrocytes in ALS and provides insights into the pathological mechanisms.
MOLECULAR NEURODEGENERATION
(2023)
Article
Clinical Neurology
Alberto Catanese, Sandeep Rajkumar, Daniel Sommer, Pegah Masrori, Nicole Hersmus, Philip Van Damme, Simon Witzel, Albert Ludolph, Ritchie Ho, Tobias M. Boeckers, Medhanie Mulaw
Summary: Catanese et al. used a multiomics approach to study ALS, identifying a mutation-independent disease signature and providing insights into the convergent pathomechanisms of different mutations. This work contributes to our understanding of ALS by revealing common transcriptional and epigenetic alterations in the disease.
Article
Neurosciences
Brett N. Adey, Johnathan Cooper-Knock, Ahmad Al Khleifat, Isabella Fogh, Philip van Damme, Philippe Corcia, Philippe Couratier, Orla Hardiman, Russell McLaughlin, Marc Gotkine, Vivian Drory, Vincenzo Silani, Nicola Ticozzi, Jan H. Veldink, Leonard H. van den Berg, Mamede de Carvalho, Susana Pinto, Jesus S. Mora S. Pardina, Monica Povedano Panades, Peter M. Andersen, Markus Weber, Nazli A. Basak, Christopher E. Shaw, Pamela J. Shaw, Karen E. Morrison, John E. Landers, Jonathan D. Glass, Patrick Vourc'h, Richard J. B. Dobson, Gerome Breen, Ammar Al-Chalabi, Ashley R. Jones, Alfredo Iacoangeli
Summary: This study explores the relationship between CAV1/2 genes and ALS. The expression of CAV1 and CAV2 genes is found to be higher in ALS patients compared to controls, and carriers of CAV1/2 enhancer mutations show improved survival and slower progression of the disease.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Clinical Neurology
Robert McFarlane, Miriam Galvin, Mark Heverin, Eanna Mac Domhnaill, Deirdre Murray, Dara Meldrum, Peter Bede, Anthony Bolger, Lucy Hederman, Sinead Impey, Gaye Stephens, Ciara O'Meara, Vincent Wade, Ammar Al Chalabi, Adriano Chio, Phillippe Corcia, Philip van Damme, Caroline Ingre, Christopher McDermott, Monica Povedanos, Leonard Van den Berg, Orla Hardiman
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Article
Cell Biology
Joke De Vocht, Donatienne Van Weehaeghe, Fouke Ombelet, Pegah Masrori, Nikita Lamaire, Martijn Devrome, Hilde Van Esch, Mathieu Moisse, Michel Koole, Patrick Dupont, Koen Van Laere, Philip Van Damme
Summary: This study examined the impact of ALS-causing gene mutations on cerebral glucose metabolism using genetic testing and FDG PET imaging. The results showed distinctive differences in glucose metabolism patterns between C9orf72-ALS patients and sporadic ALS patients, particularly in specific regions of the brain.
Article
Clinical Neurology
Grzegorz Walkiewicz, Alicja Ronisz, Rita Van Ginderdeuren, Sophie Lemmens, Femke H. Bouwman, Jeroen J. M. Hoozemans, Tjado H. J. Morrema, Annemieke J. Rozemuller, Frederique J. Hart de Ruyter, Lies De Groef, Ingeborg Stalmans, Dietmar Rudolf Thal
Summary: This study reveals the presence of a distinct primary retinal tauopathy that is different from tauopathies in the brain. The stage of retinal p-tau pathology is correlated with age, AD, and inflammation, while vision impairment is associated with underlying eye diseases and the stage of retinal p-tau pathology.
ALZHEIMERS & DEMENTIA
(2023)
Article
Hematology
Rozenn Quarck, Lynn Willems, Birger Tielemans, Leanda Stoian, Alicja Ronisz, Allard Wagenaar, Frederic Perros, Guido Claessen, Agnieszka Ciarka, Laurent Godinas, Catharina Belge, Marc Jacquemin, Marion Delcroix
Summary: The crucial role of angiogenesis in clot resolution and fibrothrombotic obstruction of the pulmonary arterial bed in CTEPH was validated using a rabbit model. Inhibiting intrathrombus angiogenesis resulted in elevated pulmonary arterial pressure, increased pulmonary vascular resistance, and right ventricular hypertrophy, accompanied by pulmonary vessel remodeling and inflammation.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Cell Biology
Pernille Bogetofte Thomasen, Alena Salasova, Kasper Kjaer-Sorensen, Lucie Woloszczukova, Josef Lavicky, Hande Login, Jeppe Tranberg-Jensen, Sergio Almeida, Sander Beel, Michaela Kavkova, Per Qvist, Mads Kjolby, Peter Lund Ovesen, Stella Nolte, Benedicte Vestergaard, Andreea-Cornelia Udrea, Lene Niemann Nejsum, Moses Chao, Philip Van Damme, Jan Krivanek, Jeremy Dasen, Claus Oxvig, Anders Nykjaer
Summary: SorCS2 is a receptor for PGRN that plays an important role in MN diversification and axon outgrowth, as well as affecting neuromuscular junction morphology and fish motility. Deficiency of SorCS2 disrupts cell-fate decisions of brachial MNs and leads to innervation deficits of posterior nerves. In addition, SorCS2 knockout mice exhibit slower motor nerve regeneration. The interaction between primitive macrophages expressing high levels of PGRN and SorCS2-positive motor axons is crucial for axon pathfinding.
Article
Neurosciences
Jimmy Beckers, Arun Kumar Tharkeshwar, Laura Fumagalli, Matilde Contardo, Evelien Van Schoor, Raheem Fazal, Dietmar Rudolf Thal, Siddharthan Chandran, Renzo Mancuso, Ludo Van Den Bosch, Philip Van Damme
Summary: In this study, iPSC-derived MNs from C9orf72-ALS patients and isogenic control lines were used to investigate the underlying mechanisms of autophagy-lysosome pathway dysregulation. The results showed that C9orf72 loss-of-function had minimal influence on autophagy-lysosome pathway phenotypes, but primarily caused impairment in endosome maturation. Moreover, increased phosphorylation of TBK1 at S172 was observed in MNs derived from C9orf72-ALS patients.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Pediatrics
Johannes Devos, Koenraad Devriendt, Jute Richter, Katrien Jansen, Marcella Baldewijns, Dietmar R. Thal, Michael Aertsen
Summary: This report presents the neuroimaging findings of a genetically confirmed case of fetal-onset Alexander disease, with pathological correlation after termination of pregnancy. Fetal brain magnetic resonance imaging in the third trimester is shown to be a valuable tool for diagnosing fetal-onset Alexander disease in suspected cases, in addition to neurosonography. Diffuse signal abnormalities in the periventricular white matter, thickening of the fornix and optic chiasm, as well as atypical findings such as microcephaly and cortical folding abnormalities, contribute to the phenotypic variability of Alexander disease.
PEDIATRIC RADIOLOGY
(2023)
Article
Multidisciplinary Sciences
Sriram Balusu, Katrien Horre, Nicola Thrupp, Katleen Craessaerts, An Snellinx, Lutgarde Serneels, Dries T'Syen, Iordana Chrysidou, Amaia M. Arranz, Annerieke Sierksma, Joel Simren, Thomas K. Karikari, Henrik Zetterberg, Wei-Ting Chen, Dietmar Rudolf Thal, Evgenia Salta, Mark Fiers, Bart De Strooper
Summary: Neuronal cell loss is a defining feature of Alzheimer's disease (AD), and this study reveals that the up-regulation of long noncoding RNA MEG3 is strongly associated with AD. The overexpression of MEG3 induces necroptosis in human neurons, leading to significant neuronal cell loss. However, down-regulating MEG3 or inhibiting necroptosis could rescue neuronal cell loss in a mouse model of AD, suggesting potential therapeutic approaches for AD.