Article
Genetics & Heredity
Karolina Pierzynowska, Magdalena Podlacha, Dorota Luszczek, Estera Rintz, Lidia Gaffke, Zuzanna Szczudlo, Marta Tomczyk, Ryszard T. Smolenski, Grzegorz Wegrzyn
Summary: This study identified abnormal hair morphology as a potential simple marker for testing therapeutic effects or disease progression in widely used HD mouse models R6/1 and R6/2.
Article
Biochemistry & Molecular Biology
Roberto Speziale, Camilla Montesano, Giulia Di Pietro, Daniel Oscar Cicero, Vincenzo Summa, Edith Monteagudo, Laura Orsatti
Summary: Huntington's disease (HD) is a genetic condition caused by the expansion of a specific sequence in the huntingtin gene. There is a lack of effective treatments for HD, highlighting the need for reliable mouse models for preclinical studies. This study utilized a urinary liquid chromatography-high-resolution mass spectrometry analysis to identify metabolic changes in different HD mouse models, aiming to improve our understanding of the disease and identify potential biomarkers.
Article
Neurosciences
Estibaliz Etxeberria-Rekalde, Saioa Alzola-Aldamizetxebarria, Stefanie Flunkert, Isabella Hable, Magdalena Daurer, Joerg Neddens, Birgit Hutter-Paier
Summary: Researchers conducted a comprehensive analysis of R6/2 mice, identifying Ctip2 and TSPO as new markers associated with the motor system and early neuroinflammation, providing a new direction for the study of HD.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Nutrition & Dietetics
Guangsu Zhu, Min Guo, Jianxin Zhao, Hao Zhang, Gang Wang, Wei Chen
Summary: Alzheimer's disease is characterized by global metabolic alterations, leading to cognitive impairment. This study found that B. breve CCFM1025 intervention can restore the metabolic changes induced by Aβ injection, particularly in amino acid metabolism.
Article
Neurosciences
S. M. Holley, K. D. Oikonomou, C. M. Swift, L. Mohan, B. Matthews, O. Vega, G. Mkrtchyan, C. Cepeda, M. S. Levine
Summary: As Huntington's disease progresses, there is a loss of neurons in the striatum and thinning of the cerebral cortex. This study found reduced connectivity between thalamic cells and their targeted cortical regions in a mouse model of HD, suggesting impaired thalamocortical information transmission.
Article
Multidisciplinary Sciences
Marie Katrin Bondulich, Yilan Fan, Yeojin Song, Flaviano Giorgini, Gillian P. Bates
Summary: KMO depletion in HD mice can normalize dysregulated KP genes in peripheral tissues and increase levels of neuroprotective metabolites, but it does not improve behavioral phenotypes. Peripheral inflammation levels, including pro-inflammatory cytokines, are modulated by KMO deletion, suggesting a potential role in HD pathogenesis.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Jean-Baptiste Perot, Marina Celestine, Marco Palombo, Marc Dhenain, Sandrine Humbert, Emmanuel Brouillet, Julien Flament
Summary: In this study, the researchers found early defects in diffusion properties in the anterior part of the corpus callosum in a mouse model of Huntington's disease. They also observed later defects in glutamate exchange saturation transfer in the same region, as well as adjacent regions. Additionally, reductions in glutamate exchange saturation transfer were found in the frontal and piriform cortices, as well as the pallidum. These findings suggest the potential role of white matter in the brain dysfunction associated with Huntington's disease and highlight the importance of glutamate exchange saturation transfer and diffusion tensor imaging as biomarkers.
HUMAN MOLECULAR GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Masayo Hashimoto, Kenichi Watanabe, Kan Miyoshi, Yukako Koyanagi, Jun Tadano, Izuru Miyawaki
Summary: The study in the R6/2 mouse model revealed disturbances in histidine metabolism in brain tissue, as well as differential metabolites related to arginine and cysteine metabolism. Additionally, dysregulation of lipid metabolism was identified, indicating a wide range of metabolic alterations in the brain of R6/2 mice.
Article
Neurosciences
Julien Gasser, Gaelle Gillet, Jorge S. Valadas, Laura Rouviere, Apoorva Kotian, Wenqiang Fan, James Keaney, Irena Kadiu
Summary: This study found that Huntington's disease leads to brain infiltration of peripheral lymphoid and myeloid cells, resulting in activation of microglia and enhanced phagocytic functions, which in turn contribute to synaptic loss. Similar observations were made in human Huntington's disease brains. Overall, targeting microglial functions related to synaptic surveillance and pruning may have therapeutic benefits in attenuating cognitive decline and psychiatric symptoms of Huntington's disease.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Carlos Benitez Villanueva, Hans J. T. Stephensen, Rajmund Mokso, Abdellatif Benraiss, Jon Sporring, Steven A. Goldman
Summary: This study investigates the relationship between astroglial cells and medium spiny neurons (MSN) synapses in Huntington's disease (HD). The results show that HD astrocytes have impaired connection and function with synaptic sites compared to normal astrocytes, leading to striatal hyperexcitability and the development of HD.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Neurosciences
Katerina D. Oikonomou, Elissa J. Donzis, Minh T. N. Bui, Carlos Cepeda, Michael S. Levine
Summary: The study using the R6/2 mouse model found that the amplitude of somatic calcium transients in CPNs of Huntington's disease patients was reduced, but compensated by increased decay times, so that transient areas were similar between genotypes. Ryanodine receptors (RyRs) and L-type calcium channels may be potential targets for therapeutic intervention.
JOURNAL OF NEUROPHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Carlos Vicente-Gutierrez, Nicolo Bonora, Daniel Jimenez-Blasco, Irene Lopez-Fabuel, Georgina Bates, Michael P. Murphy, Angeles Almeida, Juan P. Bolanos
Summary: The study found that modulating mROS levels in neurons can prevent motor discoordination caused by neurotoxins, while modulation in astrocytes showed no beneficial effect. This indicates that the impact of modifying mROS production on mouse behavior depends on the specific cell type where they are generated.
Article
Biochemistry & Molecular Biology
Yujing Guo, Sheng Yong, Yuzhen Xu, Ying Hu, Jidong Li, Qifu Long, Xiaojun Wang, Cunlin Gu, Zengqiang Miao
Summary: High-altitude hypoxia stress is the main cause of high-altitude pulmonary edema and spleen contraction. This study investigates the key molecular profiles involved in spleen response to high altitude hypoxia using proteomics and metabolomics. The results suggest that the arachidonic acid metabolism pathway potentially promotes spleen hypoxia response. This study provides important evidence for the rational design of new therapies targeting spleen using arachidonic acid metabolism.
Article
Biochemical Research Methods
Yingying Shi, Daling Ding, Liwei Liu, Zhuolun Li, Lihua Zuo, Lin Zhou, Quzheng Du, Ziwei Jing, Xiaojian Zhang, Zhi Sun
Summary: This study identified metabolic signatures in blood and urine associated with glioma, linking them to gene expression and pathways related to the disease. Specific changes in gene expression and correlation with metabolites were revealed, indicating a potential target for developing effective therapies. Integration of metabolomics with transcriptomics provided valuable insights into the molecular perturbations underlying glioma.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Cell Biology
Akanksha Baharani, Zelan Wei, William J. Roesler, Darrell D. Mousseau
Summary: In this study, the researchers investigated kinase activity patterns and signal cascades in neural tissues of the R6/2 transgenic mouse model of Huntington's disease. They identified changes in several signaling pathways, as well as the involvement of the Rho-Rac GTPase cascade in cytoskeleton organization. The study also revealed higher levels of phosphorylated Ser138-profilin in embryonic R6/2 mouse samples, which decreased progressively during postnatal symptomatic stages.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Andreas Mund, Fabian Coscia, Andras Kriston, Reka Hollandi, Ferenc Kovacs, Andreas-David Brunner, Ede Migh, Lisa Schweizer, Alberto Santos, Michael Bzorek, Soraya Naimy, Lise Mette Rahbek-Gjerdrum, Beatrice Dyring-Andersen, Jutta Bulkescher, Claudia Lukas, Mark Adam Eckert, Ernst Lengyel, Christian Gnann, Emma Lundberg, Peter Horvath, Matthias Mann
Summary: Deep Visual Proteomics combines machine learning, automated image analysis and single-cell proteomics to link protein abundance to complex cellular or subcellular phenotypes while preserving spatial context. It successfully identifies distinct cell states with proteomic profiles and reveals spatial proteome changes in cancer progression.
NATURE BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lili Niu, Maja Thiele, Philipp E. Geyer, Ditlev Nytoft Rasmussen, Henry Emanuel Webel, Alberto Santos, Rajat Gupta, Florian Meier, Maximilian Strauss, Maria Kjaergaard, Katrine Lindvig, Suganya Jacobsen, Simon Rasmussen, Torben Hansen, Aleksander Krag, Matthias Mann
Summary: This study used mass spectrometry analysis to investigate the liver and plasma proteomics of patients with alcohol-related liver disease. Noninvasive biomarkers associated with early stages of disease progression were identified. Machine learning models revealed that these biomarkers could accurately detect fibrosis and inflammation, and predict future liver-related events and all-cause mortality.
Review
Biochemistry & Molecular Biology
Jens Andersen, Arne Schousboe
Summary: Glutamine plays an essential role in cerebral metabolism, including ammonia homeostasis, energy metabolism, and neurotransmitter recycling. The balance of cerebral glutamine is regulated by the metabolic coupling of neurons and astrocytes, and disruptions in this balance are associated with various neurological diseases. Decreased astrocyte glutamine synthesis can lead to a deficiency in metabolic substrates and precursors for neurotransmitter synthesis in neurons, resulting in synaptic dysfunction.
NEUROCHEMICAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Jens Andersen, Emil W. Westi, Elliott S. Neal, Blanca Aldana, Karin Borges
Summary: Ketogenic diets and medium-chain triglycerides play important roles in the treatment of neurological disorders, with their metabolites serving as auxiliary brain fuels in different cell types without notable competition.
NEUROCHEMICAL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Jens V. Andersen, Arne Schousboe, Petrine Wellendorph
Summary: Synaptic regulation of GABA, the primary inhibitory neurotransmitter, is crucial for brain function. Astrocytes play fundamental roles in regulating synaptic GABA signaling by removing excess GABA from the synapse and using it as a metabolic substrate for glutamine synthesis. The flow of GABA and glutamine between neurons and astrocytes, known as the GABA-glutamine cycle, is essential for maintaining inhibitory signaling.
ESSAYS IN BIOCHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Jens V. Andersen, Arne Schousboe
Summary: Since the recognition of glutamate and GABA as principal neurotransmitters, significant discoveries have been made about their synaptic homeostasis. The glutamate/GABA-glutamine cycle, involving the recycling between neurons and astrocytes, plays a crucial role in maintaining synaptic transmission. The metabolic function of neurons and astrocytes is closely related to the glutamate/GABA-glutamine cycle, with astrocytes providing metabolic support for neurons. The review focuses on cellular uptake, metabolism, and recycling of glutamate and GABA, as well as their role in brain pathology and the potential of targeting astrocyte metabolism for intervention.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Jens V. Andersen, Emil W. Westi, Nane Griem-Krey, Niels H. Skotte, Arne Schousboe, Blanca I. Aldana, Petrine Wellendorph
Summary: This study investigated the role of CaMKIIa in brain energy and neurotransmitter metabolism using a genetic knockout mouse model. The results showed that the oxidative metabolism of glucose in the cerebral cortex was significantly reduced in the absence of CaMKIIa, while the metabolism of acetate, primarily reflecting astrocyte metabolism, was unaffected. Additionally, the metabolism of glutamate in the excitatory system was impaired, while the metabolism of GABA was unaffected. These findings suggest that CaMKIIa signaling plays a metabolic role in cellular energy and neurotransmitter metabolism in the brain.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Neurosciences
Emil W. Westi, Jens Andersen, Blanca I. Aldana
Summary: Disrupted brain metabolism is crucial for neurodegenerative diseases, and the energy metabolism of neurons and astrocytes through the glutamate/GABA-glutamine cycle plays a vital role in neurotransmitter recycling. Isotope tracing, a technique to monitor cellular metabolism, has helped elucidate the mechanistic involvement of altered brain metabolism in disease progression. This review discusses the advantages, drawbacks, and applications of isotope tracing in different cerebral preparations and narrates how it has facilitated the discovery of central metabolic features in neurodegeneration, particularly in the metabolic cooperation between neurons and astrocytes.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Multidisciplinary Sciences
Pietro Fontana, Sara C. Buch-Larsen, Osamu Suyari, Rebecca Smith, Marcin J. Suskiewicz, Kira Schutzenhofer, Antonio Ariza, Johannes Gregor Matthias Rack, Michael L. Nielsen, Ivan Ahel
Summary: ADP-ribosylation signalling plays a crucial role in the DNA damage response of mammals, and its mechanism in fruit flies has been established using a multidisciplinary approach. Ser-ADPr is the major form of ADP-ribosylation in the DNA damage response of Drosophila melanogaster, and its formation depends on the dParp1:dHpf1 complex. The findings suggest that fruit flies are valuable model organisms to study the physiological role of Ser-ADPr signalling.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Emil P. T. Hertz, Ignacio Alonso-de Vega, Thomas Kruse, Yiqing Wang, Ivo A. Hendriks, Anna H. Bizard, Ania Eugui-Anta, Ronald T. Hay, Michael L. Nielsen, Jakob Nilsson, Ian D. Hickson, Niels Mailand
Summary: Hertz et al. use CRISPR screening to identify genetic vulnerabilities to inhibition of SUMOylation in human cells. They show that SUMO exerts its essential role in cell proliferation via NIP45- and BTRR-PICH-mediated DNA catenane resolution pathways. NIP45 mediates a TOP2-independent DNA catenane resolution process through its SUMO-like domains, promoting SUMOylation of specific factors including the SLX4 multi-nuclease complex, which contributes to catenane conversion into DSBs. Their findings establish the importance of SUMOylation in enabling resolution of toxic DNA catenanes via non-epistatic NIP45- and BTRR-PICH-dependent pathways to prevent mitotic failure.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Review
Biology
A. S. Rebak, I. A. Hendriks, M. L. Nielsen
Summary: Citrullination is an important post-translational modification of arginine, with roles in autoimmune disorders, innate immunity response, and stem cell potency maintenance. However, our understanding of citrullination is not as comprehensive as other post-translational modifications. High-resolution mass spectrometry provides an unbiased approach to study citrullination and has already provided valuable insights. There is still untapped potential for proteome-wide investigations of citrullination using mass spectrometry approaches.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
Meeli Mullari, Nicolas Fossat, Niels H. Skotte, Andrea Asenjo-Martinez, David T. Humphreys, Jens Bukh, Agnete Kirkeby, Troels K. H. Scheel, Michael L. Nielsen
Summary: The authors present the Brain-pCLAP methodology, identify the RBP atlas of the mouse brain, and demonstrate the differential binding of the splicing factor RBM5 to Huntington's disease relevant transcripts in R6/2 mice. Overall, they provide insights into the role of RBPs in RNA processing and their association with neurodegeneration. Rating: 8 points.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Frederick Richards, Marta J. Llorca-Cardenosa, Jamie Langton, Sara C. Buch-Larsen, Noor F. Shamkhi, Abhishek Bharadwaj Sharma, Michael L. Nielsen, Nicholas D. Lakin
Summary: The authors identify that PARP1 maintains genome integrity by regulating replication fork recovery through break-induced replication. Mechanistically, this is achieved through MRE11-dependent PARP1 activation and site-specific ADP-ribosylation of PolD3. PARP1 and PARP2 also have a novel role in regulating Rad52-dependent replication fork repair, suppressing replication-associated DNA damage, and maintaining genome stability.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Laura Mikel Mcnair, Jens Velde Andersen, Helle Sonderby Waagepetersen
Summary: This study reveals fundamental alterations in cellular energy and neurotransmitter metabolism in the aging brain, which may contribute to age-related hippocampal deficits.
NEUROCHEMISTRY INTERNATIONAL
(2023)