Article
Biochemistry & Molecular Biology
Mari Suzuki, Kazunori Sango, Yoshitaka Nagai
Summary: Alpha-synuclein plays a major role in the pathogenesis of Parkinson's disease, and fruit fly models expressing alpha-synuclein contribute to the understanding of disease-associated factors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Eiji Inoue, Takahiro Suzuki, Yasuharu Shimizu, Keiichi Sudo, Haruhisa Kawasaki, Norio Ishida
Summary: Saffron and its constituent crocetin have been found to inhibit the progression of PD in animal models, showing effects such as improving climbing ability, extending lifespan, and providing cytoprotection.
Article
Multidisciplinary Sciences
Angela Bononi, Qian Wang, Alicia A. Zolondick, Fang Bai, Mika Steele-Tanji, Joelle S. Suarez, Sandra Pastorino, Abigail Sipes, Valentina Signorato, Angelica Ferro, Flavia Novelli, Jin-Hee Kim, Michael Minaai, Yasutaka Takinishi, Laura Pellegrini, Andrea Napolitano, Ronghui Xu, Christine Farrar, Chandra Goparaju, Cristian Bassi, Massimo Negrini, Ian Pagano, Greg Sakamoto, Giovanni Gaudino, Harvey I. Pass, Jose N. Onuchic, Haining Yang, Michele Carbone
Summary: This study investigates the paradoxical finding that individuals with germline BAP1 mutations develop less aggressive mesotheliomas. The research shows that biallelic BAP1 mutations result in a reduction of HIF-1 alpha activity in mesothelioma cells and hypoxic tissues, leading to reduced aggressiveness and improved survival in these patients.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Ana Sierra-Magro, Fernando Bartolome, David Lozano-Munoz, Jesus Alarcon-Gil, Elena Gine, Marina Sanz-SanCristobal, Sandra Alonso-Gil, Marta Cortes-Canteli, Eva Carro, Ana Perez-Castillo, Jose A. Morales-Garcia
Summary: Parkinson's disease (PD) is a neurodegenerative disorder caused by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The transcription factor CCAAT/Enhancer Binding Protein beta (C/EBP beta) may be a good therapeutic target for PD treatment due to its altered levels in neurodegenerative diseases. A list of PD-related genes regulated by C/EBP beta was generated, including mitochondrial transcription factor A (TFAM). The absence of C/EBP beta may lead to the accumulation of non-functional mitochondria due to impaired autophagy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Biochemistry & Molecular Biology
Alexander Pietras
Summary: A newfound deubiquitinase has been identified to differentially stabilize HIF-2alpha in stem-like glioblastoma cells, shedding light on the regulation of hypoxic response in various tissues and cancers.
Article
Biochemistry & Molecular Biology
Adrianna Moszynska, Maciej Jaskiewicz, Marcin Serocki, Aleksandra Cabaj, David K. Crossman, Sylwia Bartoszewska, Magdalena Gebert, Michal Dabrowski, James F. Collawn, Rafal Bartoszewski
Summary: The cellular adaptive response to hypoxia is regulated by hypoxia-inducible factors (HIFs), HIF-1 and HIF-2. miRNAs play a significant role in modulating cellular signaling pathways during the hypoxic adaptive response.
Article
Biochemistry & Molecular Biology
Francesco Agostini, Luigi Bubacco, Sasanka Chakrabarti, Marco Bisaglia
Summary: Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the loss of dopaminergic neurons and accumulation of alpha-synuclein. Recent evidence suggests the involvement of iron-dependent cell death pathway, ferroptosis, in the pathogenesis of PD. This study using a Drosophila melanogaster model of PD demonstrated that over-expression of alpha-synuclein leads to protein aggregate accumulation and dopaminergic neurodegeneration, which are worsened by decreased glutathione levels or increased iron concentrations.
Article
Cell Biology
Zhiguo Niu, Jianing Fan, Fengzhe Chen, Huijie Yang, Xin Li, Ting Zhuang, Chunlei Guo, Qi Cao, Jian Zhu, Hui Wang, Qingsong Huang
Summary: Breast cancer is the most common malignancy in women globally. Abnormal expression of RBCK1 protein in breast tumors makes it a valuable diagnostic marker and drug target. Hypoxic regions in breast cancer activate the HIF1 pathway, influencing tumor recurrence and metastasis. Targeting RBCK1 could be a promising treatment strategy for ER-positive breast cancer.
CELL DEATH & DISEASE
(2022)
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
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.
Article
Oncology
Chang W. Song, Hyunkyung Kim, Haeun Cho, Mi-Sook Kim, Sun-Ha Paek, Heon-Joo Park, Robert J. Griffin, Stephanie Terezakis, Lawrence Chinsoo Cho
Summary: High-dose hypofractionated radiation stimulates anti-tumor immune response but also increases immune suppression mediated by HIF alpha. Inhibition of HIF-1 alpha can restore radiation-induced anti-tumor immunity. Combination of HIF-1 alpha inhibitors with immune checkpoint blocking antibodies may enhance overall anti-tumor immune profile.
Article
Biochemistry & Molecular Biology
Song Chen, Yejinpeng Wang, Yaoyi Xiong, Tianchen Peng, Mengxin Lu, Lian Zhang, Zhongqiang Guo
Summary: The study found that wild-type IDH1 could inhibit the proliferation and migration of RCC cells, as well as promote apoptosis, while the mutant IDH1 lacked this biological function. Additionally, the study verified the correlation between IDH1 and hypoxia signal-related proteins, and the potential role of α-KG in RCC treatment.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Cell Biology
Qin Lin, Zheng Chen, Wei Shi, Zeheng Lv, Xiaoping Wan, Kun Gao
Summary: In this study, we found that JAK1 was frequently mutated and downregulated in EC. Knockdown of JAK1 promoted EC cell proliferation and migration, while overexpression of JAK1 reduced EC cell proliferation and migration. Unexpectedly, the hypoxia inducible factor (HIF) pathway was activated in JAK1-depleted EC cells. Mechanistically, JAK1 interacted with HIF-1/2 alpha and reduced their protein expression under hypoxia. Knockdown of HIF-1/2 alpha reversed the growth and migration induced by JAK1 knockdown in EC cells under hypoxia. JAK1 knockdown or pharmacological inhibition of JAK1 kinase activity upregulated transcription of HIF target genes under hypoxia, while JAK1 overexpression downregulated transcription of HIF target genes under hypoxia.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Biochemistry & Molecular Biology
Yijie Wang, Xiong Liu, Min Wang, Yu Wang, Shuo Wang, Lai Jin, Min Liu, Jun Zhou, Yan Chen
Summary: This study reveals that UBE3B is an E3 ligase for HIF-2 & alpha; and its depletion inhibits breast cancer progression. UBE3B physically interacts with HIF-2 & alpha; and promotes its polyubiquitination, thereby inhibiting its degradation. UBE3B depletion also inhibits breast cancer cell proliferation, migration, and invasion, and suppresses tumor growth and metastasis.
Article
Medicine, Research & Experimental
Emad Samaan, Nehal M. Ramadan, Hoda M. M. Abdulaziz, Dina Ibrahim, Mohamed El-Sherbiny, Rana Elbayar, Yasmin Ghattas, Joly Abdlmalek, Omnia Bayali, Yousef Elhusseini, Aya Maghrabia, Randa El -Gamal
Summary: Both vildagliptin and empagliflozin treatment could delay the progression of diabetic nephropathy through their differential modulating effects on the PHD3/HIF-2 alpha pathway, with better efficacy observed for SGLT2i.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Biology
Lucy Granat, Rachel J. Hunt, Joseph M. Bateman
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2020)
Article
Neurosciences
Ryan J. H. West, Chris Ugbode, Laura Fort-Aznar, Sean T. Sweeney
NEUROBIOLOGY OF DISEASE
(2020)
Article
Biochemistry & Molecular Biology
Chris Ugbode, Nathan Garnham, Laura Fort-Aznar, Gareth J. O. Evans, Sangeeta Chawla, Sean T. Sweeney
Article
Clinical Neurology
Alexander Bampton, Ariana Gatt, Jack Humphrey, Sara Cappelli, Dipanjan Bhattacharya, Sandrine Foti, Anna-Leigh Brown, Yasmine Asi, Yi Hua Low, Marco Foiani, Towfique Raj, Emanuele Buratti, Pietro Fratta, Tammaryn Lashley
Summary: Heterogeneous nuclear ribonucleoproteins (HnRNPs) play crucial roles in nucleic acid metabolism, with HnRNP K mislocalisation in neurodegenerative diseases such as frontotemporal lobar degeneration and aging being associated with widespread splicing changes.
ACTA NEUROPATHOLOGICA
(2021)
Article
Neurosciences
Tiffany S. Cho, Egle Beigaite, Nathaniel E. Klein, Sean T. Sweeney, Martha R. C. Bhattacharya
Summary: TMEM184B mutation results in abnormal neuromuscular structure and behavioral defects in mice. By studying the closely related gene Tmep in Drosophila, researchers found that Tmep plays a critical role in synaptic transmission and locomotor behavior by regulating synaptic excitability and membrane trafficking at the neuromuscular junction. The findings suggest that Tmep is necessary for proper locomotion and synaptic function, and its dysregulation can lead to neuromuscular defects.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Clinical Neurology
Rahul Sidhu, Ariana Gatt, Pietro Fratta, Tammaryn Lashley, Alexander Bampton
Summary: This study reveals that nuclear depletion and cytoplasmic mislocalisation of hnRNP K are common neuropathological features in FTLD and elderly control brain. Furthermore, the dentate nucleus of the cerebellum is also vulnerable to hnRNP K mislocalisation. The findings suggest that hnRNP K dysfunction may have broader relevance to neurodegeneration and ageing.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2022)
Review
Biochemical Research Methods
Theo Issitt, Laura Wiggins, Martin Veysey, Sean T. Sweeney, William J. Brackenbury, Kelly Redeker
Summary: Volatile compounds in human breath can reflect the inner workings of the body, but the identification of breath biomarkers remains inconsistent and conflicting. This study grouped volatile organic compounds into chemical functional groups to improve biomarker discovery. The results show that using targeted functional volatile biomarkers, rather than individual compounds, can improve accuracy and success in diagnostic research and application.
JOURNAL OF BREATH RESEARCH
(2022)
Article
Multidisciplinary Sciences
Anna-Leigh Brown, Oscar G. Wilkins, Matthew J. Keuss, Sarah E. Hill, Matteo Zanovello, Weaverly Colleen Lee, Alexander Bampton, Flora C. Y. Lee, Laura Masino, Yue A. Qi, Sam Bryce-Smith, Ariana Gatt, Martina Hallegger, Delphine Fagegaltier, Hemali Phatnani, Jia Newcombe, Emil K. Gustavsson, Sahba Seddighi, Joel F. Reyes, Steven L. Coon, Daniel Ramos, Giampietro Schiavo, Elizabeth M. C. Fisher, Towfique Raj, Maria Secrier, Tammaryn Lashley, Jernej Ule, Emanuele Buratti, Jack Humphrey, Michael E. Ward, Pietro Fratta
Summary: Risk variants in the synaptic gene UNC13A are associated with increased risk of ALS and FTD. These variants lead to the inclusion of a cryptic exon in UNC13A when TDP-43 is depleted, resulting in the loss of UNC13A protein. Two common UNC13A polymorphisms strongly associated with ALS and FTD risk overlap with TDP-43 binding sites.
Article
Biochemistry & Molecular Biology
Theo Issitt, Sean T. Sweeney, William J. Brackenbury, Kelly R. Redeker
Summary: Volatile compounds in breath can be used to diagnose and monitor medical conditions, but conflicting results have limited the adoption of this diagnostic approach. This study presents a novel method for volatile sampling from breath, using multi-time-point analysis and ambient air subtraction to effectively measure compound flux as a proxy for active metabolism. This approach could be used for biomarker discovery and diagnosis of diseases.
Review
Neurosciences
Marie Girodengo, Sila K. Ultanir, Joseph M. Bateman
Summary: This article discusses recent studies that have deepened our understanding of the key roles of the mTOR pathway in human nervous system development and disease. Advances in single-cell transcriptomics and cerebral organoid technology have revealed specific functions of mTOR signaling in human cortical development and its mis-regulation in neurodevelopmental disorders.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Pranetha Baskaran, Simeon R. Mihaylov, Elin Vinsland, Kriti Shah, Lucy Granat, Sila K. Ultanir, Andrew R. Tee, Jernej Murn, Joseph M. Bateman
Summary: The RNA-binding protein Unkempt is identified as a novel substrate of mTORC1, which is regulated by nutrient levels and growth factors. Unkempt is phosphorylated by mTORC1 through its interaction with the regulatory-associated protein Raptor. Phosphorylation within a serine-rich region in the C-terminal half of Unkempt affects its ability to regulate cellular morphogenesis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Genetics & Heredity
Lucy Granat, Debbra Knorr, Daniel T. Ranson, Emma Hamer, Ram Prosad S. Chakrabarty, Francesca M. Mattedi, Laura P. Fort-Aznar, Frank Hirth, Sean P. Sweeney, Alessio Vagnoni, Navdeep P. Chandel, Joseph Bateman
Summary: Mutations in subunits of the mitochondrial NADH dehydrogenase cause severe neurological diseases and death in infancy. The underlying mechanisms and effective treatments for complex I deficiency remain poorly understood. By studying Drosophila with complex I deficiency, it was found that neuronal deficiency leads to locomotor defects, seizures, reduced lifespan, mitochondrial morphology defects, reduced endoplasmic reticulum-mitochondria contacts, and activation of the endoplasmic reticulum unfolded protein response (UPR) in neurons.
Meeting Abstract
Clinical Neurology
Alexander Bampton, Ariana Gatt, Jack Humphrey, Dipanjan Bhattacharya, Sara Cappelli, Emanuele Buratti, Pietro Fratta, Tammaryn Lashley
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Meeting Abstract
Clinical Neurology
Ariana Gatt, Alex Bampton, Jack Humphrey, Sara Cappelli, Emanuele Buratti, Pietro Fratta, Tammaryn Lashley
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)