Review
Cell Biology
Venturina Stagni, Alessandra Ferri, Claudia Cirotti, Daniela Barila
Summary: There is a strong interplay between autophagy and genomic stability, with recent evidence linking DNA Damage Response (DDR) and autophagy in influencing cell fate. ATM kinase plays a crucial role in balancing senescence and apoptosis in response to stimuli, and its aberrant deregulation is linked to the development of pathologies like cancer and neurodegeneration.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Majd Haj, Amit Levon, Yann Frey, Noa Hourvitz, Judith Campisi, Yehuda Tzfati, Ran Elkon, Yael Ziv, Yosef Shiloh
Summary: The genetic disorder A-T is caused by loss of the homeostatic protein kinase ATM and leads to genome instability, tissue degeneration, cancer predisposition, and premature aging. Lowering the oxygen concentration to a physiological level range significantly extends the proliferative lifespan of A-T fibroblasts, but they still undergo premature senescence and exhibit high genome instability. Senescing A-T fibroblasts show distinct transcriptional dynamics, including activation of interferon-stimulated genes and altered expression of genes associated with extracellular matrix remodeling.
Article
Cell Biology
Beimeng Yang, Xiuli Dan, Yujun Hou, Jong-Hyuk Lee, Noah Wechter, Sudarshan Krishnamurthy, Risako Kimura, Mansi Babbar, Tyler Demarest, Ross McDevitt, Shiliang Zhang, Yongqing Zhang, Mark P. Mattson, Deborah L. Croteau, Vilhelm A. Bohr
Summary: The study shows that mitochondrial dysfunction and cellular senescence occur in A-T patient fibroblasts, ATM-deficient cells, and mice, and boosting intracellular NAD(+) levels can prevent senescence and senescence-associated secretory phenotype (SASP) by promoting mitophagy in a PINK1-dependent manner. This suggests a central role for mitochondrial dysfunction-induced senescence in A-T pathogenesis and highlights enhancing mitophagy as a potential therapeutic intervention.
Editorial Material
Neurosciences
Erica L. Gorenberg, James Shorter
Summary: The study identified the RNAs sequestered by tau inclusions and showed related perturbations in nuclear speckles.
Article
Immunology
Raissa Bernardes da Silva, Willian dos Reis Bertoldo, Lucila Langoni Naves, Fernanda Bernadelli de Vito, Jeziel Dener Damasceno, Luiz Ricardo Orsini Tosi, Carlos Renato Machado, Andre Luiz Pedrosa
Summary: In this study, the DNA damage response pathways in promastigote forms of L. major were investigated. The overexpression of LmjEXO1 made the cells more susceptible to genotoxic damage, while ATR-specific inhibition made the control cells more susceptible to oxidative damage.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Shengyan Gao, Matthew Esparza, Ishmael Dehghan, Vasilisa Aksenova, Ke Zhang, Kimberly Batten, Max B. Ferretti, Bridget E. Begg, Tolga Cagatay, Jerry W. Shay, Adolfo Garcia-Sastre, Elizabeth J. Goldsmith, Zhijian J. Chen, Mary Dasso, Kristen W. Lynch, Melanie H. Cobb, Beatriz M. A. Fontoura
Summary: This study reveals that the cellular protein kinase TAO2 plays a critical role in the formation and function of nuclear speckles. Depletion or inhibition of TAO2 disrupts nuclear speckle structure and decreases the levels of proteins involved in nuclear speckle assembly and splicing, leading to compromised splicing and nuclear export of influenza virus M mRNA and inhibition of viral replication.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Lorna W. Harries
Summary: The human genome produces a wide range of proteins and non-coding RNAs through the coordinated processes of mRNA processing and metabolism. Dysfunctional RNA processing and metabolism have been implicated in cellular senescence and may be a key contributor to aging.
Article
Genetics & Heredity
Sara Biagiotti, Ambra Barone, Mattia Paolo Aliano, Giulia Federici, Marco Malatesta, Caterina Caputi, Silvia Soddu, Vincenzo Leuzzi, Luciana Chessa, Mauro Magnani
Summary: Most ATM variants associated with Ataxia Telangiectasia are classified as variants with uncertain significance. This study focused on a specific ATM variant found in Lebanese brothers, revealing it to be pathogenic even though it causes an atypical phenotype. Dexamethasone showed therapeutic potential on this and possibly other missense ATM variants.
FRONTIERS IN GENETICS
(2021)
Article
Oncology
R. Kim, M. Kwon, M. An, S. T. Kim, S. A. Smith, A. B. Loembe, P. G. S. Mortimer, J. Armenia, N. Lukashchuk, N. Shah, E. Dean, W. -Y. Park, J. Lee
Summary: Ceralasertib in combination with durvalumab has promising antitumor activity among patients with metastatic melanoma who have failed anti-programmed cell death protein 1 therapy, and shows stable and sustained disease control rate.
ANNALS OF ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Julio Gutierrez, Karel H. M. van Wely, Carlos Martinez-A
Summary: Background mRNA processing is important for gene expression, and its dysfunction can cause physiological disorders. The gene Dido1 has been identified as a stemness marker involved in embryonic stem cell differentiation. Deletion of an exon of Dido1 in mice leads to early embryonic death, while mice lacking DIDO3 survive but develop mild hepatitis, testicular degeneration, and ataxia.
CELL AND BIOSCIENCE
(2022)
Article
Cell Biology
Julio Aguado, Harman K. Chaggar, Cecilia Gomez-Inclan, Mohammed R. Shaker, Hannah C. Leeson, Alan Mackay-Sim, Ernst J. Wolvetang
Summary: Ataxia-telangiectasia (A-T) is a genetic disorder caused by the lack of functional ATM kinase, leading to chronic inflammation and premature aging in the central nervous system. The cGAS-STING pathway is shown to play a crucial role in recognizing micronuclei and inducing senescence-associated secretory phenotype (SASP) in A-T cells and brain organoids, making it a novel therapeutic target for treating neuropathology in A-T patients.
Review
Biochemistry & Molecular Biology
Goutham Narayanan Subramanian, Abrey Jie Yeo, Magtouf Hnaidi Gatei, David John Coman, Martin Francis Lavin
Summary: The ATM protein kinase has diverse functions in the cell, including protecting DNA, maintaining cellular homeostasis, and safeguarding against external and internal damage.
Article
Medical Laboratory Technology
Chunyu Gu, Hong Wang, Jianbo Shu, Jie Zheng, Dong Li, Chunquan Cai, Peiyuan Zhang
Summary: This study described atypical symptoms of A-T in a 5-year-old girl and proposed a dual-omics diagnostic approach combining RNA-seq with WES. The study also discussed phenotypic heterogeneity of A-T among family members and individuals.
CLINICA CHIMICA ACTA
(2021)
Review
Health Care Sciences & Services
Sharon A. McGrath-Morrow, Cynthia C. Rothblum-Oviatt, Jennifer Wright, Haley Schlechter, Maureen A. Lefton-Greif, Valerie A. Natale, Thomas O. Crawford, Howard M. Lederman
Summary: Ataxia telangiectasia (A-T) is a rare autosomal recessive disease characterized by progressive ataxia, oculocutaneous telangiectasias, and immune system impairment. Patients with A-T have an increased risk of malignancy, leading to premature death.
JOURNAL OF MULTIDISCIPLINARY HEALTHCARE
(2021)
Review
Cell Biology
Julio Aguado, Cecilia Gomez-Inclan, Hannah C. Leeson, Martin F. Lavin, Yosef Shiloh, Ernst J. Wolvetang
Summary: Ataxia-telangiectasia (A-T) is a complex disorder characterized by progressive cerebellar degeneration, immunodeficiency, radiation sensitivity, genome instability, and predisposition to cancer. The premature aging component of A-T is of great importance in driving the disease.
AGEING RESEARCH REVIEWS
(2022)
Article
Biotechnology & Applied Microbiology
Danae Siderakou, Evangelia Zilelidou, Sofia Poimenidou, Spiros Paramithiotis, Eleni Mavrogonatou, Georgia Zoumpopoulou, Ioanna Tsipra, Dimitris Kletsas, Effie Tsakalidou, Panagiotis N. Skandamis
Summary: This study finds that sublethally injured L.monocytogenes cells retain virulence and surface attachment potential, highlighting the importance of considering sublethally injured cells in terms of food safety.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Dentistry, Oral Surgery & Medicine
Dimitrios Kloukos, Eleni Mavrogonatou, Dimitris Kletsas, Polyzois Makras, George Koukos, Andreas Stavropoulos, Christos Katsaros
Summary: This study aimed to investigate the fluctuation of bone turnover markers in the gingival crevicular fluid and serum of orthodontic patients. The results revealed no significant changes in these markers during the initial stages of orthodontic treatment.
EUROPEAN JOURNAL OF ORTHODONTICS
(2022)
Correction
Cell Biology
Dimitris Veroutis, Anastasios Kouroumalis, Nefeli Lagopati, Aikaterini Polyzou, Christos Chamilos, Stavroula Papadodima, Konstantinos Evangelou, Vassilis G. G. Gorgoulis, Dimitris Kletsas
MECHANISMS OF AGEING AND DEVELOPMENT
(2022)
Review
Cell Biology
Panagiotis Chandris, Christina C. Giannouli, George Panayotou
Summary: This article provides an overview of available tools for monitoring the dynamics of biochemical reactions and the kinetics of metabolites, and discusses the potential for developing new methodologies that combine classical biochemistry with advanced imaging.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biophysics
Charles A. Kenworthy, Nayem Haque, Shu-Hao Liou, Panagiotis Chandris, Vincent Wong, Patrycja Dziuba, Luke D. Lavis, Wei-Li Liu, Robert H. Singer, Robert A. Coleman
Summary: Chromatin remodeler PBAF can dynamically target different chromatin states within a live cell and cycles on and off chromatin hubs, with bromodomains potentially playing a direct role in nucleosome remodeling.
BIOPHYSICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Fani Vlachou, Aimilia Varela, Konstantina Stathopoulou, Konstantinos Ntatsoulis, Evgenia Synolaki, Harris Pratsinis, Dimitris Kletsas, Paschalis Sideras, Constantinos H. Davos, Yassemi Capetanaki, Stelios Psarras
Summary: Galectin-3 plays a role in promoting cardiac adverse remodeling, inflammation, and failure by affecting functions of cardiac fibroblasts and macrophages. This study suggests that Galectin-3 is a valid intervention target for treating heart failure and associated comorbidities.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemical Research Methods
Christophoros Christophoridis, Anastasios Kouroumalis, Dimitris Kletsas
Summary: Low back pain is a common chronic musculoskeletal disorder caused by the degeneration of the intervertebral discs (IVDs). The accumulation of bisphosphonates, such as zoledronic acid (ZOL), in the IVDs and their physiological role has not been studied extensively. This study developed and validated an analytical method for quantifying ZOL in various tissues, and found that ZOL accumulated rapidly in blood plasma and skin, but not in the nucleus pulposus, the core of the IVD.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2022)
Article
Oncology
Zoi Piperigkou, Anastasios Koutsandreas, Marco Franchi, Vasiliki Zolota, Dimitrios Kletsas, Alberto Passi, Nikos K. Karamanos
Summary: Estrogen receptors (ERs) play a pivotal role in the development and progression of triple-negative breast cancer (TNBC). This study investigates the exact role of ER beta in the progression of TNBC. The findings suggest that targeting ER beta may be a promising approach for managing the metastatic dynamics of TNBC breast cancer.
FRONTIERS IN ONCOLOGY
(2022)
Article
Dentistry, Oral Surgery & Medicine
Harris Pratsinis, Spyridon N. Papageorgiou, Nearchos Panayi, Anna Iliadi, Theodore Eliades, Dimitris Kletsas
Summary: This study investigated the biocompatibility of a 3D-printed orthodontic aligner and found that it did not show cytotoxicity or estrogenicity on human gingival fibroblasts and breast cancer cell lines. The aligner samples did not affect the intracellular levels of reactive oxygen species and did not induce significant estrogenic effects.
AMERICAN JOURNAL OF ORTHODONTICS AND DENTOFACIAL ORTHOPEDICS
(2022)
Article
Cell Biology
Eleni Mavrogonatou, Maria Angelopoulou, Sophia V. Rizou, Harris Pratsinis, Vassilis G. Gorgoulis, Dimitris Kletsas
Summary: The crucial signaling pathways regulating the survival of UVB-treated human dermal fibroblasts were investigated in this study. The results showed that MAPK family members, Akt, EGFR, Nrf2, JNKs, and ATM-p53 are involved in the viability regulation. EGFR/Akt and Nrf2 act as auxiliary anti-apoptotic machineries, while JNKs/ATM-p53 activation and interplay are necessary for cellular defense and maintenance of cell viability.
CELL DEATH & DISEASE
(2022)
Article
Genetics & Heredity
Maria Papatsirou, Marios A. Diamantopoulos, Katerina Katsaraki, Dimitris Kletsas, Christos K. Kontos, Andreas Scorilas
Summary: This study identified nine novel circRNAs in breast cancer cell lines and predicted their potential involvement in tumor onset and progression based on their molecular properties.
Editorial Material
Biochemistry & Molecular Biology
Nikos Karamanos, Sylvie Ricard-Blum, Dimitris Kletsas
Article
Cell Biology
Katarzyna Malgorzata Kwiatkowska, Eleni Mavrogonatou, Adamantia Papadopoulou, Claudia Sala, Luciano Calzari, Davide Gentilini, Maria Giulia Bacalini, Daniele Dall'Olio, Gastone Castellani, Francesco Ravaioli, Claudio Franceschi, Paolo Garagnani, Chiara Pirazzini, Dimitris Kletsas
Summary: The aim of this study was to characterize DNA methylation patterns in replicative and induced senescence in different human cell types. Three epigenetic signatures were identified: cell type- and treatment-specific signature, cell type-specific senescence-related signature, and cell type-transversal replicative senescence-related signature. Cluster analysis revealed distinct DNA methylation patterns in replicative senescent cells, and enrichment in pathways related to the nervous system was shown. Despite no statistically significant evidence of age acceleration, a trend of increased biological age in replicative senescent cultures of all three cell types was observed. This work highlights the heterogeneity of senescent cells and their impact on tissue homeostasis.
Review
Cell Biology
Eleni Mavrogonatou, Adamantia Papadopoulou, Harris Pratsinis, Dimitris Kletsas
Summary: The extracellular matrix (ECM) plays a crucial role in maintaining tissue homeostasis and fighting against aging. Cellular senescence can alter the composition of ECM, and the interaction between accumulated senescent cells and ECM may contribute to age-related pathologies.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Dafni-Alexandra Kavvoura, Michalis K. Stefanakis, Dimitris Kletsas, Haralambos E. Katerinopoulos, Harris Pratsinis
Summary: This study aimed to characterize two common Cretan carob tree cultivars by assessing their essential oil, fatty acid, and carbohydrate profiles, as well as evaluate the use of deseeded pod and seed extracts for cosmetic applications. The extracts showed antioxidant, tyrosinase- and collagenase-inhibitory activities, ability to block glucose-induced AGEs, and in some cases, UVB absorbance and photoprotective activities. Seed extracts exhibited higher activity, and 30% aqueous methanol was more efficient for extraction than n-hexane. Serial partitioning yielded fractions with enriched biological activities. These Cretan carob extracts and fractions are promising candidates for use in cosmetics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)