Review
Clinical Neurology
Melissa A. E. van de Wal, Merel J. W. Adjobo-Hermans, Jaap Keijer, Tom J. J. Schirris, Judith R. Homberg, Mariusz R. Wieckowski, Sander Grefte, Evert M. van Schothorst, Clara van Karnebeek, Albert Quintana, Werner J. H. Koopman
Summary: Mitochondrial dysfunction is associated with various syndromes and diseases, including Leigh syndrome. Mutations in the NDUFS4 gene can cause Leigh syndrome, and studying it in mouse models has provided new insights into the pathomechanism and treatment.
Article
Genetics & Heredity
Marta Zawadzka, Magdalena Krygier, Malgorzata Pawlowicz, Matheus Vernet Machado Bressan Wilke, Karolina Rutkowska, Naig Gueguen, Valerie Desquiret-Dumas, Eric W. Klee, Lisa A. Schimmenti, Jaroslaw Slawek, Vincent Procaccio, Rafal Ploski, Maria Mazurkiewicz-Beldzinska
Summary: Leigh syndrome is a progressive neurodegenerative disease with extensive clinical and biochemical features. This study describes three Polish patients and provides further evidence for the association of DNAJC30 gene variants with Leigh syndrome. DNAJC30-associated Leigh syndrome exhibits clinical heterogeneity with variable age at onset, movement disorder phenotype, and blood lactate level.
Article
Anesthesiology
Kira A. Spencer, Michael Mulholland, John Snell, Miranda Howe, Katerina James, Allison R. Hanaford, Philip G. Morgan, Margaret Sedensky, Simon C. Johnson
Summary: The study found that isoflurane is toxic in the Ndufs4(-/-) model of Leigh syndrome. The toxic effects depend on the status of underlying neurologic disease, and can be prevented by the CSF1R inhibitor pexidartinib, and influenced by oxygen concentration in the carrier gas.
BRITISH JOURNAL OF ANAESTHESIA
(2023)
Review
Pediatrics
Jaewon Kim, Jaewoong Lee, Dae-Hyun Jang
Summary: Leigh syndrome is a neurodegenerative disorder characterized by neurological deterioration and various symptoms. In this case, the syndrome was caused by pathogenic variants of the NDUFAF6 gene. The patient underwent therapies but experienced progressive physical impairment.
FRONTIERS IN PEDIATRICS
(2022)
Article
Clinical Neurology
Sarah L. Stenton, Marketa Tesarova, Natalia L. Sheremet, Claudia Catarino, Valerio Carelli, Elzbieta Ciara, Kathryn Curry, Martin Engvall, Leah R. Fleming, Peter Freisinger, Katarzyna Iwanicka-Pronicka, Elzbieta Jurkiewicz, Thomas Klopstock, Mary K. Koenig, Hana Kolarova, Bohdan Kousal, Tatiana Krylova, Chiara La Morgia, Lenka Noskova, Dorota Piekutowska-Abramczuk, Sam N. Russo, Viktor Stranecky, Iveta Tothova, Frank Traisk, Holger Prokisch
Summary: The study identified 28 previously unreported individuals carrying the DNAJC30 variant, expanding the spectrum of Leber hereditary optic neuropathy and Leigh syndrome. The findings confirmed sex-dependent incomplete penetrance of the homozygous variant and the association of DNAJC30 with Leigh syndrome.
Review
Biochemistry & Molecular Biology
Ryosuke Saiki, Kan Katayama, Kaoru Dohi
Summary: Proteinuria is associated with mortality, and nephrotic syndrome is defined by proteinuria and hypoalbuminemia. Genetic kidney diseases have been discovered more frequently with advances in medicine. This review focuses on the study of proteinuria/nephrotic syndrome and other kidney diseases in mouse models, leading to significant progress in understanding genetics and pathophysiology. Future genetic analysis of proteinuric kidney disease/nephrotic syndrome may provide personalized treatment options.
Article
Genetics & Heredity
Ke Gong, Li Xie, Zhong-shi Wu, Xia Xie, Xing-xing Zhang, Jin-Lan Chen
Summary: This case study highlights the importance of gene detection in improving diagnostic accuracy, especially in developing countries like China. By identifying a PDHA1 mutation as the underlying cause of Leigh syndrome in a 12-year-old boy, and predicting changes in protein structure, the study provides valuable insights into the treatment of this genetic disorder. The patient's condition significantly improved after receiving targeted therapy.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Karin Terburgh, Janee Coetzer, Jeremy Z. Lindeque, Francois H. van der Westhuizen, Roan Louw
Summary: The study investigated brain regional respiratory chain enzyme activities and metabolic profiles in a mouse model of LS with global CI deficiency. It found that brain regions with higher residual CI activity showed less severe metabolic perturbations, suggesting potential key areas for future therapeutic intervention studies.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Neurosciences
Kevin Aguilar, Gemma Comes, Carla Canal, Albert Quintana, Elisenda Sanz, Juan Hidalgo
Summary: This study investigates the role of microglial cells in the pathology of Leigh-like syndrome and the contribution of neuroinflammation. The depletion of microglial cells extends the lifespan and delays motor symptoms in a mouse model of the disease. However, the major cytokine interleukin-6 does not significantly affect the disease progression.
Article
Gastroenterology & Hepatology
Chen Qu, Lu He, Nan Yao, Jinying Li, Yuchuan Jiang, Binkui Li, Shuang Peng, Kunpeng Hu, Dong Chen, Guo Chen, Wei Huang, Mingrong Cao, Jun Fan, Yunfei Yuan, Wencai Ye, Jian Hong
Summary: The study demonstrated that MSI2 in myofibroblasts plays a crucial role in HCC development by regulating IL-6 and IL-11 secretion, affecting cell proliferation and metastasis. Deletion of MSI2 in myofibroblasts effectively inhibited HCC progression.
Article
Clinical Neurology
Ayako Wada, Michiyuki Kawakami, Yuka Yamada, Kentaro Kaji, Nanako Hijikata, Fumio Liu, Tomoyoshi Otsuka, Tetsuya Tsuji
Summary: In this study, the Neuromuscular disease Swallowing Status Scale (NdSSS) was used to evaluate dysphagia in patients with multiple system atrophy (MSA). The study found that NdSSS has satisfactory reliability, concurrent validity, and responsiveness in assessing dysphagia in MSA patients. It also revealed that patients with a history of pneumonia have more severe dysphagia, and the risk of pneumonia is related to NdSSS stage and MSA-p.
FRONTIERS IN NEUROLOGY
(2022)
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
Cell Biology
Jin-Lan Huang, Fan Zhang, Min Su, Jiaxin Li, Wen Yi, Li-Xiang Hou, Si-Man Yang, Jin-Yuan Liu, Hao-An Zhang, Tengfei Ma, Deng-Pan Wu
Summary: The study found that MeCP2 plays a crucial role in age-related cognitive decline by regulating synaptic plasticity. MeCP2's modulation of synaptic plasticity may be associated with the CREB1 pathway, indicating it as a promising target for the treatment of age-related cognitive decline in neurodegenerative diseases.
Article
Neurosciences
Zhen-Yu Li, Li-Hua Chen, Xiu-Yun Zhao, Hong Chen, Yan-Yun Sun, Mei-Hong Lu, Zhao-Tao Wang, Mei Chen, Li Lu, Wenhui Huang, Rui Chen, De-En Xu, Ru-Xiang Xu, Quan-Hong Ma
Summary: The study demonstrates that clemastine can alleviate Alzheimer's disease pathology in APP/PS1 transgenic mice, including reducing amyloid-beta load, neuroinflammation, and cognitive deficits. Clemastine reduces Aβ generation by decreasing levels of BACE1, APP CTFs, while enhancing autophagy and suppressing the mTOR signaling pathway.
EXPERIMENTAL NEUROLOGY
(2021)
Review
Genetics & Heredity
Allison Hanaford, Simon C. Johnson
Summary: Genetic mitochondrial diseases pose a significant challenge to human health, and recent evidence suggests that the immune system plays a key role in the pathogenesis of at least some forms of these diseases.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Sport Sciences
Yvonne A. W. Hartman, Laura C. M. Tillmans, David L. Benschop, Astrid N. L. Hermans, Kevin M. R. Nijssen, Thijs M. H. Eijsvogels, Peter H. G. M. Willems, Cees J. Tack, Maria T. E. Hopman, Jurgen A. H. R. Claassen, Dick H. J. Thijssen
Summary: Long-term reduction in sedentary behavior improves peripheral vascular function and cerebral blood flow, and acutely prevents impaired vascular function and decreased cerebral blood flow. These results highlight the potential benefits of reducing sedentary behavior to acutely and chronically improve cardio- or cerebrovascular risk.
MEDICINE & SCIENCE IN SPORTS & EXERCISE
(2021)
Correction
Biochemistry & Molecular Biology
Sjoerd Verkaart, Werner J. H. Koopman, Sjenet E. van Emst-de Vries, Leo G. J. Nijtmans, Lambertus W. P. J. van den Heuvel, Jan A. M. Smeitink, Peter H. G. M. Willems
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Correction
Biochemistry & Molecular Biology
S. Verkaart, W. J. Koopman, J. Cheek, S. E. van Emst-de Vries, L. W. van den Heuvel, J. A. Smeitink, P. H. Willems
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Review
Clinical Neurology
Melissa A. E. van de Wal, Merel J. W. Adjobo-Hermans, Jaap Keijer, Tom J. J. Schirris, Judith R. Homberg, Mariusz R. Wieckowski, Sander Grefte, Evert M. van Schothorst, Clara van Karnebeek, Albert Quintana, Werner J. H. Koopman
Summary: Mitochondrial dysfunction is associated with various syndromes and diseases, including Leigh syndrome. Mutations in the NDUFS4 gene can cause Leigh syndrome, and studying it in mouse models has provided new insights into the pathomechanism and treatment.
Review
Cell Biology
Sandeep Chenna, Werner J. H. Koopman, Jochen H. M. Prehn, Niamh M. C. Connolly
Summary: This article discusses the mechanistic models and minimal models of mitochondrial reactive oxygen species (ROS) homeostasis. Mechanistic models provide valuable insights but are complex, while minimal models use a smaller set of equations to describe empirical relationships and generate hypotheses. Finally, the article illustrates the application of minimal models in studying the pathophysiology of ROS.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Elianne P. Bulthuis, Claudia Einer, Felix Distelmaier, Laszlo Groh, Sjenet E. Van Emst-De Vries, Els Van De Westerlo, Melissa Van De Wal, Jori Wagenaars, Richard J. Rodenburg, Jan A. M. Smeitink, Niels P. Riksen, Peter H. G. M. Willems, Merel J. W. Adjobo-Hermans, Hans Zischka, Werner J. H. Koopman
Summary: The study showed that targeted molecules for mitochondria can lead to decreased levels of mitochondrial complex I, reduced ETC supercomplexes, inhibition of mitochondrial oxygen consumption, increased extracellular acidification, altered mitochondrial morphology, and stimulated hydroethidine oxidation. The research highlights the impact of mitochondria-targeting moieties on cellular functions.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Elianne P. Bulthuis, Cindy E. J. Dieteren, Jesper Bergmans, Job Berkhout, Jori A. Wagenaars, Els M. A. van de Westerlo, Emina Podhumljak, Mark A. Hink, Laura F. B. Hesp, Hannah S. Rosa, Afshan N. Malik, Mariska te Lindert, Peter H. G. M. Willems, Wouter den Otter, Han J. G. E. Gardeniers, Merel J. W. Adjobo-Hermans, Werner J. H. Koopman
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2022)
Article
Microbiology
Samara Rosendo Machado, Jieqiong Qu, Werner J. H. Koopman, Pascal Miesen
Summary: This study discovered the important role of Dhx15 gene and the glycolysis pathway it regulates in controlling mosquito infection by arboviruses, providing a new perspective on the molecular interactions between arboviruses and their mosquito hosts.
Article
Toxicology
Charlotte A. Hoogstraten, Maaike M. E. Jacobs, Guido de Boer, Melissa A. E. van de Wal, Werner J. H. Koopman, Jan A. M. Smeitink, Frans G. M. Russel, Tom J. J. Schirris
Summary: Mitochondrial dysfunction plays a pivotal role in drug-induced acute kidney injury (AKI) and the transport protein AAC is an important potential drug off-target. In this study, AAC3 deficiency led to reduced mitochondrial function and mass in human renal proximal tubular cells, particularly affecting metabolic spare capacity under galactose conditions.
ARCHIVES OF TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Elianne P. Bulthuis, Cindy E. J. Dieteren, Jesper Bergmans, Job Berkhout, Jori A. Wagenaars, Els M. A. van de Westerlo, Emina Podhumljak, Mark A. Hink, Laura F. B. Hesp, Hannah S. Rosa, Afshan N. Malik, Mariska Kea-te Lindert, Peter H. G. M. Willems, Han J. G. E. Gardeniers, Wouter K. den Otter, Merel J. W. Adjobo-Hermans, Werner J. H. Koopman
Summary: Macromolecules of various sizes induce crowding in the cellular environment, which affects biochemical reactions by altering solvent viscosity, water-accessible volume, and protein properties. This study shows that the mitochondrial matrix solvent exhibits macromolecular crowding, as demonstrated by the elongated molecular structure of fluorescent protein fusion peptides and decreased diffusion constant with increasing molecular weight. Chloramphenicol treatment impairs mitochondrial function and increases matrix viscosity, indicating increased macromolecular crowding. These findings highlight the importance of matrix crowding in mitochondria and suggest that changes in crowding conditions can impact biochemical reactions.
Article
Biochemistry & Molecular Biology
Federica Conte, Angel Ashikov, Rachel Mijdam, Eline G. P. van de Ven, Monique van Scherpenzeel, Raisa Veizaj, Seyed P. Mahalleh-Yousefi, Merel A. Post, Karin Huijben, Daan M. Panneman, Richard J. T. Rodenburg, Nicol C. Voermans, Alejandro Garanto, Werner J. H. Koopman, Hans J. C. T. Wessels, Marek J. Noga, Dirk J. Lefeber
Summary: Phosphoglucomutase 1 (PGM1) is a key enzyme involved in energy metabolism and its deficiency causes a wide range of symptoms. D-galactose supplementation has been shown to improve some symptoms, but its effects on skeletal muscle and heart remain unclear. In this study, a muscle cell model for PGM1 deficiency was established, which revealed that D-galactose failed to restore the reduced energy production capacity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Meeting Abstract
Medicine, General & Internal
D. W. J. H. Koopman
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2022)
Correction
Cell Biology
W. J. H. Koopman, H. J. Visch, S. Verkaart, L. W. P. J. van den Heuvel, J. A. M. Smeitink, P. H. G. M. Willems
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
