Article
Medicine, Research & Experimental
Cedric Happi Mbakam, Joel Rousseau, Yaoyao Lu, Anne Bigot, Kamel Mamchaoui, Vincent Mouly, Jacques P. Tremblay
Summary: In this study, researchers used CRISPR-Cas9 prime editing technology to correct a mutation in the DMD gene, resulting in improved editing efficiency and restoration of dystrophin protein expression. Optimization of the reverse transcription template sequence led to a significant increase in the editing percentage of the target nucleotide.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Multidisciplinary Sciences
Michael J. Stec, Qi Su, Christina Adler, Lance Zhang, David R. Golann, Naveen P. Khan, Lampros Panagis, S. Armando Villalta, Min Ni, Yi Wei, Johnathon R. Walls, Andrew J. Murphy, George D. Yancopoulos, Gurinder S. Atwal, Sandra Kleiner, Gabor Halasz, Mark W. Sleeman
Summary: Using spatial transcriptomics and single-cell RNA sequencing datasets, a high-resolution cellular and molecular spatial atlas of the severely dystrophic D2-mdx mouse model was generated. Clustering analysis revealed the nonuniform distribution of unique cell populations associated with multiple regenerative timepoints, faithfully recapitulating the asynchronous regeneration observed in human DMD muscle. Through spatiotemporal gene expression signatures, it was found that propagation of inflammatory and fibrotic signals from locally damaged areas contributes to widespread pathology and identifying targetable pathways for DMD therapy within discrete microenvironments. Overall, this spatial atlas of dystrophic muscle provides a valuable resource for studying DMD disease biology and therapeutic target discovery.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Zsofia Onodi, Petra Lujza Szabo, Daniel Kucsera, Peter Pokreisz, Christopher Dostal, Karlheinz Hilber, Gavin Y. Oudit, Bruno K. Podesser, Peter Ferdinandy, Zoltan V. Varga, Attila Kiss
Summary: Duchenne muscular dystrophy (DMD) is a muscle wasting disease characterized by difficulty moving and premature death, mainly due to heart failure. Inflammation is thought to play a role in the disease progression, but the specific mechanisms are not well understood.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Shanshan Yao, Zihao Chen, Yuanyuan Yu, Ning Zhang, Hewen Jiang, Ge Zhang, Zongkang Zhang, Baoting Zhang
Summary: Duchenne muscular dystrophy is a lethal neuromuscular disorder caused by the absence of dystrophin protein, with no cure currently available. The standard of care involves glucocorticoids treatments for symptom relief. Therapeutic strategies focus on restoring dystrophin function and targeting downstream pathological changes like inflammation and fibrosis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Clinical Neurology
Giulio Gadaleta, Guido Urbano, Chiara Brusa, Rossella D'Alessandro, Enrica Rolle, Ilaria Cavallina, Alessio Mattei, Fulvia Ribolla, Claudia Raineri, Stefano Pidello, Liliana Vercelli, Federica S. Ricci, Tiziana E. Mongini
Summary: The clinical characteristics of adults with DMD include mechanical ventilation, swallowing and nutritional issues, and bone density alterations. Other issues include respiratory infections, gastrointestinal symptoms, metabolic acidosis, psychiatric symptoms, and chronic pain. Patients have a negative perception of their physical health but a more positive assessment of their mental health.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Review
Biochemistry & Molecular Biology
Katarzyna Kazirod, Malgorzata Myszka, Jozef Dulak, Agnieszka Loboda
Summary: Hydrogen sulfide (H2S), known as a poisonous gas, has recently been found to play important roles in physiological and pathological processes. Although H2S has been shown to have cytoprotective effects through modulation of various responses, its role in skeletal muscle pathophysiology is not well understood. However, H2S-based therapy has the potential to attenuate the progression of Duchenne muscular dystrophy (DMD) and other muscle-related disorders.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Sharon Mordechay, Shaun Smullen, Paul Evans, Olga Genin, Mark Pines, Orna Halevy
Summary: The study showed that the enantiomers of halofuginone had differential effects on motor coordination and muscle histopathology in mdx mice, with (+)-halofuginone being the most effective. These findings suggest a potential use for (+)-halofuginone as a therapy for DMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Thomas Taetzsch, Dillon Shapiro, Randa Eldosougi, Tracey Myers, Robert E. Settlage, Gregorio Valdez
Summary: The absence of miR-133b exacerbates the dystrophic phenotype of DMD-afflicted skeletal muscle by dysregulating muscle stem cells, inflammation, and fibrosis. Deletion of miR-133b influences muscle fiber regeneration, satellite cell proliferation and differentiation, and leads to widespread transcriptomic changes in mdx muscle, demonstrating its role in mitigating the deleterious effects of DMD.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Pharmacology & Pharmacy
Zeren Sun, Dengqiu Xu, Lei Zhao, Xihua Li, Sijia Li, Xiaofei Huang, Chunjie Li, Lixin Sun, Bing Liu, Zhenzhou Jiang, Luyong Zhang
Summary: The study found that fenofibrate can promote the differentiation of myofibers by down-regulating the expression of myostatin protein in myoblasts, significantly improving muscle function and reducing muscle damage in mdx mice, along with anti-inflammatory effects.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Francesca Paoletti, Franci Merzel, Alberto Cassetta, Iza Ogris, Sonia Covaceuszach, Joze Grdadolnik, Doriano Lamba, Simona Golic Grdadolnik
Summary: NGF plays a crucial role in the maintenance and growth of neuronal populations, with interactions with ATP impacting the binding to specific receptors. The study suggests that ATP may serve as a transient molecular modulator of NGF signaling in health and disease states.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Immunology
Brigida Boccanegra, Ornella Cappellari, Paola Mantuano, Daniela Trisciuzzi, Antonietta Mele, Lisamaura Tulimiero, Michela De Bellis, Santa Cirmi, Francesca Sanarica, Alessandro Giovanni Cerchiara, Elena Conte, Ramona Meanti, Laura Rizzi, Elena Bresciani, Severine Denoyelle, Jean-Alain Fehrentz, Gabriele Cruciani, Orazio Nicolotti, Antonella Liantonio, Antonio Torsello, Annamaria De Luca
Summary: Growth hormone secretagogues (GHSs) have multiple actions including activation of GHS-receptor 1a, control of inflammation and metabolism, enhancement of GH/IGF-1-mediated myogenesis, and inhibition of angiotensin-converting enzyme. This study provides preclinical evidence for the potential benefits of GHSs in Duchenne muscular dystrophy (DMD). The results show that GHSs can improve muscle strength, reduce fibrosis-related parameters, and improve muscle metabolism in mdx mice, suggesting that GHSs have potential as therapeutic agents for DMD.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Clinical Neurology
Craig M. Zaidman, Crystal M. Proud, Craig M. Mcdonald, Kelly J. Lehman, Natalie L. Goedeker, Stefanie Mason, Alexander P. Murphy, Maitea Guridi, Shufang Wang, Carol Reid, Eddie Darton, Christoph Wandel, Sarah Lewis, Jyoti Malhotra, Danielle A. Griffin, Rachael A. Potter, Louise R. Rodino-Klapac, Jerry R. Mendell
Summary: The study ENDEAVOR demonstrated that the commercial process delandistrogene moxeparvovec is safe and effective in improving micro-dystrophin expression in patients with Duchenne muscular dystrophy. After 12 weeks of treatment, significant improvements were observed in micro-dystrophin expression, as well as patient's functional outcomes and quality of life at 1 year.
ANNALS OF NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Angus Lindsay, John Holm, Maria Razzoli, Alessandro Bartolomucci, James M. Ervasti, Dawn A. Lowe
Summary: Research shows that mdx mice do not habituate to mild stress, and daily exposure to mild stress for weeks exacerbates phenotypes associated with dystrophinopathy in mdx mice.
Article
Cell Biology
Kantaro Yoshioka, Akira Ito, Masanobu Horie, Kazushi Ikeda, Sho Kataoka, Keiichiro Sato, Taichi Yoshigai, Hidetoshi Sakurai, Akitsu Hotta, Yoshinori Kawabe, Masamichi Kamihira
Summary: Recent research on Duchenne muscular dystrophy (DMD) has utilized induced pluripotent stem (iPS) cell models and CRISPR-Cas9 technology for gene repair, showing improved contractile activity in myotubes derived from repaired iPS cells under electrical pulse stimulation culture.
Article
Cell Biology
Elisia D. Tichy, Nuoying Ma, David Sidibe, Emanuele Loro, Jacob Kocan, Delia Z. Chen, Tejvir S. Khurana, Paul Hasty, Foteini Mourkioti
Summary: Repeated cycles of damage and repair in muscle disorders like DMD can lead to inefficiency in muscle stem cell response. The early telomere shortening in diseased MuSCs is associated with aberrant NF-kappa B activation, leading to severe skeletal muscle defects. NF-kappa B plays a role in regulating stem-cell-specific telomere length and could be a common mechanism in diseases characterized by chronic inflammation.
Article
Biochemistry & Molecular Biology
Mayra Colardo, Michele Petraroia, Letizia Lerza, Daniele Pensabene, Noemi Martella, Valentina Pallottini, Marco Segatto
Summary: This study investigated the impact of nerve growth factor (NGF) on glial cell cholesterol metabolism and neuroprotection. The results showed that NGF treatment increased the expression of proteins and enzymes involved in cholesterol metabolism in glial cells, as well as the secretion of ApoE and extracellular cholesterol levels. Moreover, NGF treatment effectively counteracted cytotoxicity caused by oxidative stress and this neuroprotective effect was dependent on glial ApoE secretion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Biochemistry & Molecular Biology
Sabrina Di Bartolomeo, Marco Segatto
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Magda Gharbiya, Giacomo Visioli, Alessandro Trebbastoni, Giuseppe Maria Albanese, Mayra Colardo, Fabrizia D'Antonio, Marco Segatto, Alessandro Lambiase
Summary: We conducted a study to evaluate the diagnostic role of AD biomarkers in tears and their association with retinal and choroidal microstructures. We found that tear A beta 1-42 levels had a high sensitivity and specificity in detecting MCI and AD patients. Additionally, A beta 1-42 levels were correlated with psychometric scores and choroidal thickness. Testing A beta 1-42 levels in tears could be a minimally invasive and cost-saving method for early detection and diagnosis of AD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Michela Zamboni, Georgios Strimpakos, Eleonora Poggiogalle, Lorenzo M. Donini, Donato Civitareale
Summary: Obesity affects thyroid gland function, leading to a higher incidence of thyroid-related diseases. However, our understanding of the molecular mechanisms involved is limited. This study provides the first experimental evidence that adipocyte signaling downregulates the expression of TTF-2/FoxE1, a crucial factor in thyroid development, homeostasis, and thyroid cancer. Both in vivo and in vitro evidence suggest that adipocyte signaling mediates the inhibition of TTF-2/FoxE1 gene expression.
JOURNAL OF MOLECULAR ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Valentina Muto, Federica Benigni, Valentina Magliocca, Rossella Borghi, Elisabetta Flex, Valentina Pallottini, Alessandro Rosa, Claudia Compagnucci, Marco Tartaglia
Summary: Induced pluripotent stem cells (iPSCs) are a reliable in vitro disease model system, especially when animal models are not available or do not accurately mimic the human pathophenotype. However, the variability in behavior of individual patient-derived clones has been a limitation. The development of CRISPR/Cas9-based gene editing has overcome this limitation by generating isogenic iPSCs with corrected genetic lesions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Mayra Colardo, Deborah Gargano, Miriam Russo, Michele Petraroia, Daniele Pensabene, Giuseppina D'Alessandro, Antonio Santoro, Cristina Limatola, Marco Segatto, Sabrina Di Bartolomeo
Summary: In this study, the effects of BET protein inhibition on GBM cell reprogramming were investigated. It was found that the BET protein inhibitor could promote the differentiation of GBM cells, impair cell proliferation, and enhance the toxicity of the drug Temozolomide. Moreover, autophagy activation was found to be necessary for the pro-differentiation capability of the BET protein.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Alice Bruscolini, Angela Iannitelli, Marco Segatto, Pamela Rosso, Elena Fico, Marzia Buonfiglio, Alessandro Lambiase, Paola Tirassa
Summary: This study investigated the correlation between the expression levels of NGF and BDNF in tears and serum and ophthalmic and psycho-cognitive symptoms in Graves' Orbitopathy (GO) patients. The results showed that NGF and BDNF expression correlated with ophthalmic symptoms, while mature/precursor NGF and BDNF correlated with psycho-cognitive variables. This study is the first to suggest that changes in NGF and BDNF processing in tears and serum may be associated with ocular and cognitive alterations in GO patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Deborah Gargano, Marco Segatto, Sabrina Di Bartolomeo
Summary: BET proteins play a key role in transcriptional regulation and cell plasticity, and they are crucial in the development and pathogenesis of glioblastoma. Epigenome dysregulation associated with loss of cellular identity and functions are emerging as important features of glioblastoma pathogenesis. BET family members could be promising targets for translational breakthroughs in glioblastoma treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Martina Parente, Claudia Tonini, Marco Segatto, Valentina Pallottini
Summary: Cholesterol, discovered over two centuries ago, plays a crucial role in human physiology and its alterations are associated with various pathologies. The search for new molecular targets and compounds to modulate cholesterol metabolism has been a focus of global research groups for many years. In addition to known regulators, new pathways have been uncovered in this important physiological process.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2023)
Article
Immunology
Matteo Caforio, Nicola Tumino, Cristina Sorino, Isabella Manni, Stefano Di Giovenale, Giulia Piaggio, Simona Iezzi, Georgios Strimpakos, Elisabetta Mattei, Lorenzo Moretta, M. Fanciulli, Paola Vacca, Franco Locatelli, Valentina Folgiero
Summary: The over-expression of AATF/Che-1 in different tumors is well-known, and its effect on tumorigenicity is mainly through controlling tumor cell proliferation and viability. However, the impact of Che-1 over-expression on the immune response has not been investigated. This study reveals that Che-1 can modulate the expression of Nectin-1 ligand at the transcriptional level, leading to the impairment of NK cell killing activity and the alteration of NK cell ligand expression.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Noemi Martella, Mayra Colardo, William Sergio, Michele Petraroia, Michela Varone, Daniele Pensabene, Miriam Russo, Sabrina Di Bartolomeo, Giancarlo Ranalli, Gabriella Saviano, Marco Segatto
Summary: Lavender essential oil (LEO) may have important hypocholesterolemic activities due to the presence of monoterpenoid and sesquiterpenoid compounds. However, the molecular mechanisms by which LEO influences cholesterol homeostasis are not well understood. This study demonstrated that LEO administration increases intracellular cholesterol content and affects the expression of proteins involved in cholesterol metabolism through the compound terpinene-4-ol.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
