Article
Multidisciplinary Sciences
Lucy C. Young, Ruby Goldstein de Salazar, Sae-Won Han, Zi Yi Stephanie Huang, Alan Merk, Matthew Drew, Joseph Darling, Vanessa Wall, Reinhard Grisshammer, Alice Cheng, Madeline R. Allison, Matthew J. Sale, Dwight V. Nissley, Dominic Esposito, Jana Ognjenovic, Frank McCormick
Summary: The majority of pathogenic mutations in the NF1 gene reduce neurofibromin protein expression, but the mechanism by which loss-of-function missense variants drive NF1 disease is less understood. Patient variants in codons 844 to 848 cause protein instability and exert a dominant-negative action, leading to destabilization of wild-type neurofibromin through protein dimerization. The cryogenic electron microscopy structure of neurofibromin has been used to predict and validate other patient variants that act through a similar mechanism, providing important implications for patient counseling, disease management, and therapeutics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Neurosciences
Majida Charif, Yvette C. Wong, Soojin Kim, Agnes Guichet, Catherine Vignal, Xavier Zanlonghi, Philippe Bensaid, Vincent Procaccio, Dominique Bonneau, Patrizia Amati-Bonneau, Pascal Reynier, Dimitri Krainc, Guy Lenaers
Summary: Inherited optic neuropathies are the most common mitochondrial diseases, with neurodegeneration and loss of retinal ganglion cells being key characteristics. Mutations in the MIEF1 gene, which encodes the MID51 protein, have been identified as a cause for a rare form of late-onset progressive optic neuropathy. These mutations disrupt mitochondrial network dynamics without affecting MID51's localization or oligomerization on the outer mitochondrial membrane. Properly regulated mitochondrial dynamics play a crucial role in neurodegeneration.
MOLECULAR NEURODEGENERATION
(2021)
Article
Cardiac & Cardiovascular Systems
Rami S. Najjar, Denise Knapp, Desiree Wanders, Rafaela G. Feresin
Summary: This study aimed to investigate the effects of berries on cardiac inflammation and oxidative stress induced by a high-fat, high-sucrose diet. The results showed that supplementation with blackberry and raspberry reduced the expression of NADPH-oxidase, increased the expression of catalase and superoxide dismutase, attenuated the activation of TLR4 signaling and NF-kB pathway, and reduced the expression of SAPK/JNK. The combination of blackberry and raspberry supplementation showed the best effects in alleviating obesity-induced cardiac inflammation and oxidative stress.
NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
(2022)
Review
Biochemistry & Molecular Biology
Anna Cozzi, Paolo Santambrogio, Maddalena Ripamonti, Ermanna Rovida, Sonia Levi
Summary: Neuroferritinopathy is a rare genetic movement disorder characterized by the production of ferritin that cannot properly manage iron, leading to harmful consequences for cells. It shares features with Neurodegeneration with Brain Iron Accumulation and also demonstrates signs of accelerated aging, making it a potentially valuable model for studying aging processes.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Cell & Tissue Engineering
Flavia Palombo, Camille Peron, Leonardo Caporali, Angelo Iannielli, Alessandra Maresca, Ivano Di Meo, Claudio Fiorini, Alice Segnali, Francesca L. Sciacca, Ambra Rizzo, Sonia Levi, Anu Suomalainen, Alessandro Prigione, Vania Broccoli, Valerio Carelli, Valeria Tiranti
Summary: This study conducted mtDNA deep sequencing during the transition of iPSCs and NPCs, finding that mtDNA variants fluctuate between appearing and disappearing with some potentially having functional implications. It strongly recommends including mtDNA analysis in the validation process of iPSCs and NPCs to ensure their certification and usability.
Review
Neurosciences
Luca Mignani, Barbara Gnutti, Daniela Zizioli, Dario Finazzi
Summary: Coenzyme A (CoA) is a vital cofactor involved in numerous biochemical processes in organisms, playing crucial roles in cell metabolism, gene expression, and redox regulation. Its biosynthesis and homeostasis are controlled by external stimuli, and disruptions are linked to various pathological conditions.
Article
Biochemistry & Molecular Biology
Ana C. Moreira, Tania Silva, Goncalo Mesquita, Ana Cordeiro Gomes, Clara M. Bento, Joao V. Neves, Daniela F. Rodrigues, Pedro N. Rodrigues, Agostinho A. Almeida, Paolo Santambrogio, Maria Salome Gomes
Summary: In Mycobacterium avium infection, macrophage FTH1 plays a key role in iron redistribution by regulating the level of available iron in tissues, thereby influencing resistance to infection and inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Gideon L. Smith, Ayush K. Srivastava, Aliaksandra A. Reutovich, Nathan J. Hunter, Paolo Arosio, Artem Melman, Fadi Bou-Abdallah
Summary: By studying the kinetics of iron release from ferritin in fresh yeast cell lysates, this study found that iron release from ferritin is faster in cell lysates compared to buffered solutions. The presence of certain cellular metabolites in yeast cell lysates facilitates the reductive release of ferric iron from the ferritin core.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Paolo Santambrogio, Maddalena Ripamonti, Anna Cozzi, Marzia Raimondi, Chiara Cavestro, Ivano Di Meo, Alicia Rubio, Stefano Taverna, Valeria Tiranti, Sonia Levi
Summary: This study established a specific newly generated astrocyte model that can recapitulate the human phenotype associated with neurodegeneration associated with defective pantothenate kinase-2. It provides insights into the pathogenetic mechanisms underlying the disease.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Anna Martina Battaglia, Alessandro Sacco, Ida Daniela Perrotta, Maria Concetta Faniello, Mariangela Scalise, Daniele Torella, Sonia Levi, Francesco Costanzo, Flavia Biamonte
Summary: This study proposes the baseline and induced intracellular free iron level as a significant determinant of ferroptosis sensitivity and discusses the potential use of ferlixit in combination with erastin to overcome ferroptosis chemoresistance in ovarian cancer.
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Marion Rosello, Malo Serafini, Luca Mignani, Dario Finazzi, Carine Giovannangeli, Marina C. Mione, Jean-Paul Concordet, Filippo Del Bene
Summary: Base Editors are emerging as an innovative technology to introduce point mutations in complex genomes. This study describes a near PAM-less base editor and its application in efficiently creating disease models in zebrafish harboring specific point mutations.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Aliaksandra A. Reutovich, Ayush K. Srivastava, Gideon L. Smith, Alexandre Foucher, Douglas M. Yates, Eric A. Stach, Georgia C. Papaefthymiou, Paolo Arosio, Fadi Bou-Abdallah
Summary: This study investigated the impact of phosphate on the kinetics, structure, and reactivity of ferritin iron cores. The results showed that phosphate significantly accelerated the oxidation and core formation of iron in ferritin, as well as influenced the size and morphology of the iron mineral. Additionally, phosphate promoted the mobilization of iron from ferritin. These findings have important implications for understanding the importance of ferritin iron management in vivo.
Article
Biochemistry & Molecular Biology
Luca Mignani, Daniela Zizioli, Deepak Khatri, Nicola Facchinello, Marco Schiavone, Giuseppe De Palma, Dario Finazzi
Summary: This research explores the phenotypic characteristics of PANK2 gene mutations in a zebrafish animal model, identifying higher vulnerability of selected cell and tissue types to pank2 deficiency. These findings provide important clues for better understanding and treating PKAN.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Biochemistry & Molecular Biology
Paolo Arosio
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Paolo Santambrogio, Anna Cozzi, Ivano Di Meo, Chiara Cavestro, Cristina Vergara, Laura Rodriguez-Pascau, Marc Martinell, Pilar Pizcueta, Valeria Tiranti, Sonia Levi
Summary: This study tested the effectiveness of the brain-penetrant peroxisome proliferator-activated receptor gamma agonist leriglitazone in ameliorating mitochondrial defects in a cellular model of Pantothenate kinase-2 associated Neurodegeneration (PKAN). The results showed that leriglitazone improved the viability and respiratory activity of PKAN cells, while reducing iron accumulation, suggesting it could be a beneficial therapeutic approach for PKAN treatment.
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)
Article
Biochemistry & Molecular Biology
Daniela Zizioli, Andrea Mastinu, Alessia Musco, Sara Anna Bonini, Dario Finazzi, Rosaria Avisani, Giovanni Battista Kron Morelli, Sergio Pecorelli, Maurizio Memo
Summary: In this study, the angiogenetic properties of purified extracts from Helix aspersa were investigated for the first time. The results showed that the snail extracts could induce angiogenesis by increasing the three well-established parameters of angiogenesis. These effects may be mediated by the vascular endothelial growth factor (VEGF) pathway.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Mohamed Boumaiza, Imene Fhoula, Fernando Carmona, Maura Poli, Michela Asperti, Alessandra Gianoncelli, Michela Bertuzzi, Paolo Arosio, Mohamed Nejib Marzouki
Summary: In this study, a chimera (HepcH) was created by fusing camel hepcidin to a human ferritin H-chain and characterized. The results showed that HepcH retained the properties of both hepcidin and ferritin, binding more iron than wild type human ferritin. It also demonstrated biological activity by specifically binding cell lines expressing ferroportin and promoting ferroportin degradation.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2022)