Article
Biochemistry & Molecular Biology
Valentina Naef, Maria Marchese, Asahi Ogi, Gianluca Fichi, Daniele Galatolo, Rosario Licitra, Stefano Doccini, Tiziano Verri, Francesco Argenton, Federica Morani, Filippo M. Santorelli
Summary: The study demonstrates that zebrafish can serve as a model organism for ARSCS, facilitating the efficient and rapid optimization and screening of potential therapeutic compounds. This finding opens up new possibilities for interventions targeting the early phases of Purkinje cell degeneration in ARSCS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Ryan A. Dohoney, Johnson A. Joseph, Charles Baysah, Alexandra G. Thomas, Apshara Siwakoti, Tyler D. Ball, Sunil Kumar
Summary: Abberent protein-protein interactions (aPPIs) play a crucial role in pathological conditions and can be targeted for therapeutic purposes. We have developed a chromatography-free method to synthesize a highly diverse chemical library of oligopyridylamides (OPs) to enhance affinity for disease-relevant targets.
ACS CHEMICAL BIOLOGY
(2023)
Article
Cell Biology
Joanne Toh, Ling Ling Chua, Patrick Ho, Edwin Sandanaraj, Carol Tang, Hongyan Wang, Eng King Tan
Summary: This study demonstrates the neuroprotective effects of LRRK2 protective variants in a Parkinson's disease fruit fly model. RNA sequencing revealed upregulation of specific gene pathways in flies carrying the pathogenic variant, which was restored in rescue phenotypes. Using protective gene variants may offer potential new therapeutic targets for aging and neurodegeneration in PD.
Article
Pharmacology & Pharmacy
Bangfu Zhu, Tom Parsons, Wenche Stensen, John S. Mjoen Svendsen, Anders Fugelli, James J. L. Hodge
Summary: Alzheimer's disease, a common neurodegenerative disease with no cure, is more prevalent in Down syndrome patients due to potential genetic factors. Research has shown that targeting DYRK1A gene with medication can reduce neurodegeneration caused by AD and DS-related genes.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Bangfu Zhu, Tom Parsons, Wenche Stensen, John S. Mjoen Svendsen, Anders Fugelli, James J. L. Hodge
Summary: Alzheimer's disease (AD) is a common neurodegenerative disease with no effective treatments. People with Down syndrome (DS) have an increased risk of AD, and DYRK1A may be a potential therapeutic target. Through studying Drosophila models, it was found that the DYRK1A inhibitor PST-001 can improve the pathological processes caused by AD and DS-associated genes.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Clinical Neurology
Melanie Lang-Orsini, Paloma Gonzalez-Perez
Summary: Mutations in nuclear-encoded genes and primary genetic defects of mitochondrial DNA are both associated with chronic progressive external ophthalmoplegia (CPEO) phenotype, but distinguishing specific causal genetic defects is difficult. In pure CPEO or CPEO plus phenotype, further investigation of nuclear DNA mutations can provide more information.
FRONTIERS IN NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Nicolas Kayser, Friedemann Zaiser, Anna C. Veenstra, Hui Wang, Burulca Gocmen, Priska Eckert, Henriette Franz, Anna Kottgen, Gerd Walz, Toma A. Yakulov
Summary: The zebrafish pronephros model, using morpholino oligonucleotides (MO) for depleting target genes, has been widely used to study human ciliopathy phenotypes. However, recent studies have found discrepancies between the results obtained from MO and genetically mutated zebrafish. This study analyzed mutations in the nphp1-4-8 module in zebrafish and found that the mutant fish exhibited similar phenotypes to those generated by MO, but at a lower frequency. The upregulation of circadian clock genes seems to play a role in ameliorating the loss of nphp genes, resulting in phenotypic differences.
HUMAN MOLECULAR GENETICS
(2022)
Article
Biochemical Research Methods
Junho Lee, Jin Su Kim, Yangjin Kim
Summary: The study investigates the interaction between cancer stem cells and tumor cells that facilitate cognitive impairment during long-term trastuzumab therapy. The developed mathematical model involving IL-6 and key apoptotic regulation reveals the potential interference of atorvastatin in the regulation process.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Cell Biology
Melissa N. Hinman, Jared Richardson, Rose A. Sockol, Eliza D. Aronson, Sarah J. Stednitz, Katrina N. Murray, J. Andrew Berglund, Karen Guillemin
Summary: The muscleblind RNA-binding proteins are crucial regulators of RNA alternative splicing and loss of their function due to sequestration by CUG or CCUG RNA repeats is responsible for myotonic dystrophy (DM). Zebrafish models with mutations in the mbnl genes showed DM-relevant physical phenotypes and alternative splicing changes. Compound mbnl mutants exhibited more severe phenotypes, indicating partially redundant functions of Mbnl proteins.
DISEASE MODELS & MECHANISMS
(2021)
Article
Biochemical Research Methods
Shimon M. Rosenthal, Tvisha Misra, Hala Abdouni, Tess C. Branon, Alice Y. Ting, Ian C. Scott, Anne-Claude Gingras
Summary: Researchers adapted proximity labeling for protein discovery in zebrafish, developing in vivo TurbolD and mini-Turbo labeling techniques. By providing biotin directly in the egg water, they demonstrated successful biotinylation of prey proteins after 12 hours, enabling time-resolved analysis of development.
MOLECULAR & CELLULAR PROTEOMICS
(2021)
Review
Biochemistry & Molecular Biology
Hui Xia, Huimin Chen, Xue Cheng, Mingzhu Yin, Xiaowei Yao, Jun Ma, Mengzhen Huang, Gang Chen, Hongtao Liu
Summary: Zebrafish is a low-cost and genetically tractable vertebrate model that can be used to investigate the interaction between gut microbiota and host. It has features such as high fecundity, external fertilization, and early optical transparency, making it a valuable tool for addressing research questions not easily addressed in other animal models.
MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Xuechao Fei, Yun Zhang, Yufei Mei, Xiangpei Yue, Wenjing Jiang, Li Ai, Yan Yu, Hongjun Luo, Hui Li, Wenhong Luo, Xu Yang, Jihui Lyv, Rongqiao He, Weihong Song, Zhiqian Tong
Summary: The dysregulation of formaldehyde (FA) is associated with the development of Alzheimer's Disease (AD), with elevated FA levels in AD patients and animal models leading to impaired cognitive functions. By degrading FA and promoting Aβ clearance, it is possible to reduce Aβ aggregation, improve neurotoxicity, and enhance cognitive function.
MOLECULAR PSYCHIATRY
(2021)
Article
Agriculture, Dairy & Animal Science
P. L. J. Monteiro, B. Gonzales, J. N. Drum, J. E. P. Santos, M. C. Wiltbank, R. Sartori
Summary: The study aimed to evaluate the factors related to anovulation in postpartum cows, discovering that longer dry periods, lower BCS, and diseases were associated with anovulation, with different sizes of anovular follicles showing varying risk factors.
JOURNAL OF DAIRY SCIENCE
(2021)
Review
Immunology
Quxing Wei, Yanyue Deng, Qianqian Yang, Angyu Zhan, Lexun Wang
Summary: Macrophages play diverse roles in physiological and pathological conditions, particularly in metabolic disorders, and have become promising targets for diagnosis and therapy. Due to their heterogeneity and polarization, the phenotypes and functions of macrophages in metabolic disorders are complex. The development of specific molecular markers in macrophage research has greatly contributed to understanding their role in metabolic disorders. This review analyzes commonly used and novel macrophage markers related to metabolic disorders, aiming to improve their utilization in research.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Savio D. Rodrigues, Mansour Karimi, Lennert Impens, Els Van Lerberge, Griet Coussens, Stijn Aesaert, Debbie Rombaut, Dominique Holtappels, Heba M. M. Ibrahim, Marc Van Montagu, Jeroen Wagemans, Thomas B. Jacobs, Barbara De Coninck, Laurens Pauwels
Summary: Agrobacterium spp. are important plant pathogens that can be genetically modified using CRISPR-mediated base editing to introduce targeted point mutations, improving the efficiency and functionality of the strains for plant transformation and gene editing. The method developed in this study has shown high efficiency and potential for future advancements in engineering Agrobacterium strains.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Ecology
Livia Pinzoni, Federica Poli, Alessandro Grapputo, Maria Berica Rasotto, Clelia Gasparini
Summary: Female reproductive fluid plays an important role in fertilization and postmating sexual selection, but its effects on the eggs have been understudied. This study shows that female reproductive fluid can extend the egg fertilization window, thereby increasing the opportunities for multiple paternity.
AMERICAN NATURALIST
(2023)
Article
Cell Biology
Chiara Galber, Simone Fabbian, Cristina Gatto, Martina Grandi, Stefania Carissimi, Manuel Jesus Acosta, Gianluca Sgarbi, Natascia Tiso, Francesco Argenton, Giancarlo Solaini, Alessandra Baracca, Massimo Bellanda, Valentina Giorgio
Summary: Mitochondrial protein IF1 binds to ATP synthase and inhibits ATP hydrolysis in ischemic tissues. It is overexpressed in tumors and acts as a pro-oncogenic protein. Study found that disruption of ATP5IF1 gene decreases colony formation and tumor mass development in HeLa cells, indicating the role of IF1 in cancer. Lack of IF1 does not affect cell proliferation or mitochondrial respiration, but sensitizes cells to opening of the permeability transition pore (PTP). IF1 binds to ATP synthase OSCP subunit in HeLa cells under oxidative phosphorylation conditions, and this interaction protects cancer cells from PTP-dependent apoptosis under normoxic conditions.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Lucia Barazzuol, Domenico Cieri, Nicola Facchinello, Tito Cali, Philip Washbourne, Francesco Argenton, Paola Pizzo
Summary: This study generated a zebrafish line with a psen2 knockout, and found that the absence of the protein does not significantly affect Notch signaling, but leads to an exaggeration of locomotor response, a decrease in ER-mitochondria contacts, and an increase in basal autophagy. The protein also plays a role in mitochondrial axonal transport, and its downregulation reduces organelle flux in zebrafish sensory neurons. These findings highlight zebrafish as a valuable model organism for studying PS2 functions and testing potential therapies for Alzheimer's disease.
Article
Biochemistry & Molecular Biology
Luca Mignani, Nicola Facchinello, Marco Varinelli, Elena Massardi, Natascia Tiso, Cosetta Ravelli, Stefania Mitola, Peter Schu, Eugenio Monti, Giuseppe Borsani, Dario Finazzi, Daniela Zizioli
Summary: In vertebrates, two homologous heterotetrameric AP1 complexes play vital roles in regulating intracellular protein sorting in a vesicle-dependent manner. These complexes, composed of four subunits (gamma, beta 1, mu 1, and sigma 1), are ubiquitously expressed and essential for development. The knockout of specific subunits in animal models demonstrated their importance in multicellular organism development, neuronal and epithelial cell specification. Mutations in genes encoding for these subunits have been associated with various human diseases, including adaptinopathies, which affect intracellular vesicular traffic. A zebrafish model with an ap1g1 knockout was used to study the molecular mechanisms underlying adaptinopathies, revealing dysregulated cell adhesion and providing potential targets for therapeutic interventions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Chiara Tesoriero, Francesca Greco, Elena Cannone, Francesco Ghirotto, Nicola Facchinello, Marco Schiavone, Andrea Vettori
Summary: Muscular dystrophies (MDs) are a group of muscle diseases characterized by progressive weakness and eventual death. Animal models, including zebrafish, have been developed to study MDs. These models have been crucial in understanding muscle development, function, and the mechanisms of MDs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Francesca Terrin, Annachiara Tesoriere, Nicoletta Plotegher, Luisa Dalla Valle
Summary: Sex hormones and genes on sex chromosomes play a crucial role in sexual differentiation, reproduction, and brain homeostasis. They are important for brain development and function, as well as the predisposition and progression of neurodegenerative diseases. This review focuses on the impact of biological sex on brain development and its role in neurodegenerative diseases, particularly Parkinson's disease. It highlights the significance of considering sex in the study of brain physiology and pathology to better understand disease etiology and develop tailored therapeutic strategies.
Article
Neurosciences
Anna Masato, Nicoletta Plotegher, Francesca Terrin, Michele Sandre, Gaia Faustini, Andrea Thor, Stephen Adams, Giulia Berti, Susanna Cogo, Federica De Lazzari, Camilla Maria Fontana, Paul Anthony Martinez, Randy Strong, Rina Bandopadhyay, Marco Bisaglia, Arianna Bellucci, Elisa Greggio, Luisa Dalla Valle, Daniela Boassa, Luigi Bubacco
Summary: Dopamine dyshomeostasis is recognized as a key factor in the degeneration of nigrostriatal neurons in Parkinson's disease (PD). It has been found that the levels of the dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) increase in experimental models and postmortem PD patients, leading to modifications of the presynaptic protein alpha Synuclein (alpha Syn). This modification triggers alpha Syn accumulation and impairs its clearance, resulting in neuronal dysfunction and motor impairment. The development of a specific antibody that detects DOPAL-modified alpha Syn in human brain tissues further supports the relevance of this interaction in PD neurodegeneration.
NPJ PARKINSONS DISEASE
(2023)
Article
Genetics & Heredity
Valeria Guglielmi, Elia Pancheri, Elena Cannone, Vincenzo Nigro, Manuela Malatesta, Andrea Vettori, Alejandro Giorgetti, Annalaura Torella, Stefania Aurino, Barbara Cisterna, Giulia Marchetto, Giuliano Tomelleri, Paola Tonin, Marco Schiavone, Gaetano Vattemi
Summary: Missense mutations in MYOT gene cause muscle diseases with different phenotypes. We identified a novel deletion (Tyr4_His9del) in MYOT gene, and found that it causes early-onset myofibrillar myopathy with distal muscle weakness. Further experiments in zebrafish embryos confirmed the importance of the amino acid sequence in myotilin protein for the sarcomeric organization of myofibers.
Article
Biochemistry & Molecular Biology
Alexandru Ionut Gilea, Martina Magistrati, Ilenia Notaroberto, Natascia Tiso, Cristina Dallabona, Enrico Baruffini
Summary: Most eukaryotes have a mitochondrial genome called mtDNA, which is replicated by the enzyme DNA polymerase ?, or Pol ?. In animals and fungi, Pol ? consists of a catalytic subunit encoded by MIP1. In humans, Pol ? is a heterotrimer composed of the catalytic subunit homolog to Mip1, encoded by POLG, and two accessory subunits. Over the past 25 years, more than 300 pathological mutations in POLG have been identified as the cause of POLG-related disorders, characterized by mtDNA deletions and depletion. This review focuses on the biochemical properties and mutations of yeast Mip1 and their impact on enzyme activity, mtDNA stability, and mutability. The use of yeast with Mip1 mutations equivalent to human ones is discussed for confirming pathogenicity, identifying phenotypic defects, and finding rescue mechanisms and compounds. The genetic interactions of other polymerases, such as Pol ?, Rev1, and Pol ?, in maintaining mtDNA stability and preventing point mutations, are also explored.
Article
Oncology
Marika Quadri, Natascia Tiso, Francesco Musmeci, Maria I. I. Morasso, Stephen R. R. Brooks, Luca Reggiani Bonetti, Rossana Panini, Roberta Lotti, Alessandra Marconi, Carlo Pincelli, Elisabetta Palazzo
Summary: This study found differential expression of CD271 in low-risk and high-risk cSCC tumors, and demonstrated that CD271 activity can decrease the proliferation and invasiveness of cSCC, while promoting tumor cell differentiation. CD271 also inhibits the metastatic process of cSCC and increases sensitivity to therapy. Therefore, CD271 may be a promising target for future pharmaceutical development.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Engineering, Biomedical
Elena Canato, Antonella Grigoletto, Ilaria Zanotto, Tommaso Tedeschini, Benedetta Campara, Giovanna Quaglio, Giuseppe Toffoli, Delia Mandracchia, Alberto Dinarello, Natascia Tiso, Francesco Argenton, Katia Sayaf, Maria Guido, Daniela Gabbia, Sara De Martin, Gianfranco Pasut
Summary: Liposomes have a significant impact on drug delivery due to their biocompatibility and versatility. The introduction of stealth liposomes, decorated with hydrophilic polyethylene glycol (PEG) molecules, has greatly enhanced the pharmacokinetic profile compared to unmodified liposomes. However, the development of effective targeted liposomes for cancer therapy remains challenging and has experienced clinical failures.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Biology
Camilla Maria Fontana, Francesca Terrin, Nicola Facchinello, Giacomo Meneghetti, Alberto Dinarello, Lisa Gambarotto, Annalisa Zuccarotto, Micol Caichiolo, Ginevra Brocca, Ranieri Verin, Francesca Nazio, Oliana Carnevali, Francesco Cecconi, Paolo Bonaldo, Luisa Dalla Valle
Summary: This study suggests that silencing of the ambra1b gene leads to a reduction in primordial germ cells (PGCs), resulting in the development of all-male zebrafish. Injection of ambra1b and human AMBRA1 mRNA can rescue the loss of PGCs, indicating the involvement of the CUL4-DDB1 complex in PGC protection. Additionally, Ambra1 is found to have a function in the ovary of mammals as well.
BIOLOGICAL RESEARCH
(2023)
Article
Cell Biology
Rudy Celeghin, Giovanni Risato, Giorgia Beffagna, Marco Cason, Maria Bueno Marinas, Mila Della Barbera, Nicola Facchinello, Alice Giuliodori, Raquel Branas Casas, Micol Caichiolo, Andrea Vettori, Enrico Grisan, Stefania Rizzo, Luisa Dalla Valle, Francesco Argenton, Gaetano Thiene, Natascia Tiso, Kalliopi Pilichou, Cristina Basso
Summary: Arrhythmogenic cardiomyopathy (AC) is a hereditary disorder characterized by ventricular myocardium loss, and a zebrafish model can be used to study this disease and test environmental factors and candidate drugs. Our mutated zebrafish displayed cardiac alterations and signaling dysregulation, which can be worsened by intensive physical training. Treating the mutated larvae with a drug targeting the Wnt/β-catenin signaling pathway rescued the cardiac abnormalities and stabilized heart rhythm.
CELL DEATH DISCOVERY
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Marco Cason, Maria Bueno Marinas, Rudy Celeghin, Riccardo Bariani, Monica De Gaspari, Stefania Rizzo, Gaetano Thiene, Martina Perazzolo Marra, Domenico Corrado, Cristina Basso, Barbara Bauce, Kalliopi Pilichou
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)