Review
Toxicology
Benjamin J. Lang, Martin E. Guerrero, Thomas L. Prince, Yuka Okusha, Cristina Bonorino, Stuart K. Calderwood
Summary: Cells respond to protein-damaging stress by activating the Heat Shock Response (HSR), which plays a crucial role in determining cell survival or death. The modulation of HSR and its network have become attractive treatment strategies for neurodegenerative diseases and cancers. A detailed understanding of the mechanisms of HSR is necessary for the development of effective therapies, as important features of HSR continue to be uncovered.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Multidisciplinary Sciences
Marie Corteggiani, Nadege Bossuet-Greif, Jean-Philippe Nougayrede, Deborah Byrne, Marianne Ilbert, Sebastien Dementin, Marie-Therese Giudici-Orticoni, Vincent Mejean, Eric Oswald, Olivier Genest
Summary: Chaperone proteins, such as Hsp90, play a critical role in maintaining protein homeostasis in all living cells. Recent studies have shown that bacterial Hsp90 is essential for the survival of bacteria under stress conditions and is involved in the virulence of pathogenic bacteria. In this study, the researchers used site-directed mutagenesis to disrupt the binding between Hsp90 and the chaperone protein DnaK, and found that this collaboration is crucial for the folding of client proteins in bacteria. They also demonstrated that this collaboration between Hsp90 and DnaK in bacteria has evolved to form a more complex collaboration between Hsp70 and Hsp90 in eukaryotes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Pharmacology & Pharmacy
Evren Onay Ucar, Aslihan Sengelen, Elif Mertoglu Kamali
Summary: The study reveals that heat shock response (HSR) is closely related to therapeutic resistance of gliomas. Resveratrol (RSV) shows potential as an experimental agent for glioblastoma (GB) therapy, but the role of heat shock proteins (Hsps) in RSV efficacy remains unclear. The findings suggest that silencing Hsp27, Hsp60, Hsp70, and Hsp90 makes glioma cells more sensitive to RSV treatment, making these Hsps potential therapeutic targets for GB treatment.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Horticulture
Chao Gong, Qiangqiang Pang, Zhiliang Li, Zhenxing Li, Riyuan Chen, Guangwen Sun, Baojuan Sun
Summary: Under high temperature stress, Hsf and Hsp gene families are activated in eggplant cells, enhancing thermotolerance by removing denatured proteins. Specifically, upon exposure to heat stress, the majority of Hsf and Hsp genes in eggplant show increased expression levels.
Review
Oncology
Christian Tibor Josef Magyar, Yogesh K. Vashist, Deborah Stroka, Corina Kim-Fuchs, Martin D. Berger, Vanessa M. Banz
Summary: HSP90 inhibitors may have potential efficacy in the treatment of gastrointestinal cancers, but more research is needed to determine which patient subgroups and at what time point these inhibitors may be beneficial.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Veterinary Sciences
Samuel A. Atkin, Abu Saleh Md Moin, Stephen L. Atkin, Alexandra E. Butler
Summary: This study investigated the effects of hypoglycemia on the heat shock-related protein pathway. The results showed that hypoglycemia significantly decreased the expression of HSP90, 70, 27, and ubiquitin proteins, which are important for the protective response against heat stress.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Stan W. van Wijk, Kennedy S. Ramos, Bianca J. J. M. Brundel
Summary: Atrial fibrillation (AF) is the most common age-related cardiac arrhythmia globally, with current therapy being moderately effective and unable to prevent progression. Research indicates that AF persistence is related to electropathology and proteostasis imbalance. Heat shock proteins (HSPs) play a crucial role in preventing AF and have therapeutic potential, as well as potential as biomarkers to differentiate between AF stages and recurrence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Nadia Vertti-Quintero, Simon Berger, Xavier Casadevall i Solvas, Cyril Statzer, Jillian Annis, Peter Ruppen, Stavros Stavrakis, Collin Y. Ewald, Rudiyanto Gunawan, Andrew J. DeMello
Summary: The study demonstrates that protein homeostasis maintenance is a major factor influencing the heterogeneity in HSR dynamics, with individuals with enhanced protein homeostasis fidelity living longer in early adulthood. Age-related decline in protein homeostasis shows a stochastic-onset in day-1 and day-2 adult C. elegans, increasing the heterogeneity in HSR capacity. Additionally, C. elegans embryos exhibit higher HSR and proteostasis capacity compared to young adults, showing a transgenerational contribution to HSR heterogeneity dependent on maternal age.
Article
Neurosciences
Abderrezak Bouchama, Mamoon Rashid, Shuja Shafi Malik, Saeed Al Mahri, Yara Yassin, Mashan Abdullah, Nour Abdulmalek, Fuad Maashi, Abdulaziz Mashi, Altaf Khan, Badriah Alotaibi, Cynthia Lehe, Sameer Mohammad, Haitham Alkadi, Deemah Al Waadani, Saber Yezli
Summary: An evolutionary heat shock response (HSR) protects most living species, including humans, from heat-induced macromolecular damage. However, its role in the pathogenesis of heat stroke is unknown. We examined the whole genome transcriptome in peripheral blood mononuclear cells of subjects who developed heat stroke versus those who did not. The findings reveal the molecular signature of heat stroke and suggest that a powerful HSR may not be sufficient to protect against heat injury.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Cell Biology
Philip Kaenel, Gundula A. Noll, Katrin Schroedter, Elke Naffin, Julia Kronenberg, Franziska Busswinkel, Richard M. Twyman, Christian Klaembt, Dirk Pruefer
Summary: Proteostasis, the balance of protein synthesis, trafficking, and degradation, plays a crucial role in cellular function and aging. The authors found that ectopic expression of the tobacco PEBP NtFT4 in Drosophila melanogaster extended lifespan and improved locomotor decline associated with aging. NtFT4 influenced proteome maintenance through physical interactions and transcriptional regulation, including the prolonged expression of HSP26 gene, which maintained protein integrity and contributed to longevity.
Review
Biochemistry & Molecular Biology
Anastasia V. Poznyak, Varvara A. Orekhova, Vasily N. Sukhorukov, Victoria A. Khotina, Mikhail A. Popov, Alexander N. Orekhov
Summary: Atherosclerosis is a global health problem, leading to increased morbidity and mortality from cardiovascular diseases. Effective measures for prevention and treatment have not been developed yet. Understanding molecular interactions and the role of heat shock proteins in the progression of atherosclerosis is crucial. Some heat shock proteins have antiatherosclerotic effects, while others' roles are unclear. This review focuses on the antiatherosclerotic activity of specific heat shock proteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Alice Lippi, Anita Krisko
Summary: As organisms age, errors accumulate and cause problems in cellular homeostasis. However, protection and repair mechanisms, such as chaperone networks, are activated to maintain cellular proteostasis. This review focuses on the cross-organelle stress response (CORE), which coordinates a cell-wide response to compartmentalized proteotoxicity and plays a crucial role in cell survival, longevity and potential pharmacological targeting of age-related diseases.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2022)
Article
Biology
Marina Telonis-Scott, Zeinab Ali, Sandra Hangartner, Carla M. Sgro
Summary: The coordinated transcriptional selection response of Hsp70 and stv isoforms in Drosophila lines selected for heat tolerance suggests a shared regulatory hierarchy resulting in increased chaperone output accompanying increased heat tolerance. This highlights the complexity and specificity of the heat shock response in D. melanogaster, providing new avenues to examine mechanisms underlying phenotypic responses to selection for heat tolerance.
JOURNAL OF THERMAL BIOLOGY
(2021)
Article
Cell Biology
Karl M. Glastad, Julian Roessler, Janko Gospocic, Roberto Bonasio, Shelley L. Berger
Summary: In this study, the researchers investigate the role of heat shock responses mediated by hsalHSF2 in extending the longevity and survival of reproductive gamergate ants. They show that the increased heat stress resilience and life span benefits observed in gamergates can be transferred to fruit flies through the expression of hsalHSF2. The study sheds light on the mechanisms underlying the extended life span of gamergates, highlighting the significance of hsalHSF2 in ant longevity. It also underscores the importance of proteostasis in health and aging, as well as the potential for facultative life span extension in ants.
GENES & DEVELOPMENT
(2023)
Article
Virology
Jing Rin Huang, Jun Arii, Mansaku Hirai, Mitsuhiro Nishimura, Yasuko Mori, Felicia Goodrum
Summary: This study reveals that the nuclear matrix protein encoded by the U37 gene of human herpesvirus 6A (HHV-6A) activates the heat shock element promoter, leading to the accumulation of heat shock proteins. It interacts with heat shock transcription factor 1 (HSF1) and induces its phosphorylation. Inhibiting the heat shock response decreases viral protein accumulation and replication.
JOURNAL OF VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Qin Su, Sybrin P. Schroder, Lindsey T. Lelieveld, Maria J. Ferraz, Marri Verhoek, Rolf G. Boot, Herman S. Overkleeft, Johannes M. F. G. Aerts, Marta Artola, Chi-Lin Kuo
Summary: Glucocerebrosidase (GBA) plays a crucial role in hydrolyzing xylosides and transxylosylation of cholesterol. Genetic defects in GBA are associated with Gaucher disease and Parkinson's disease. Activity-based protein profiling with fluorescent probes can selectively visualize GBA and other retaining glycosidases.
Article
Chemistry, Multidisciplinary
Faezeh Nami, Maria Joao Ferraz, Thomas Bakkum, Johannes M. F. G. Aerts, Anjali Pandit
Summary: This study reports a method for tracking microbial fermentation, lipid metabolism, and structural dynamic changes using nuclear magnetic resonance (NMR) technology. The results show that lipolysis under dark and anoxia conditions leads to the breakdown of cell and organelle membranes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Nicholas G. S. McGregor, Chi-Lin Kuo, Thomas J. M. Beenakker, Chun-Sing Wong, Wendy A. Offen, Zachary Armstrong, Bogdan Florea, Jeroen D. C. Codee, Herman S. Overkleeft, Johannes M. F. G. Aerts, Gideon J. Davies
Summary: Researchers have synthesized beta-manno-configured cyclophellitol and its analogues for detecting exo-beta-mannosidases. These probes selectively label exo-beta-mannosidases from different GH families and structural studies confirm their mechanism of action.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Martijn J. C. van der Lienden, Jan Aten, Rolf G. Boot, Marco van Eijk, Johannes M. F. G. Aerts, Chi-Lin Kuo
Summary: This study investigates the impact of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) supplementation on the processing, lysosomal degradation, and total cellular enzyme level of GCase. It is found that HEPES supplementation reduces the maturation of other lysosomal enzymes and increases GCase activity in fibroblasts derived from Gaucher disease (GD) patients, complicating the use of cultured cells for diagnosing GD.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Lindsey T. Lelieveld, Sophie Gerhardt, Saskia Maas, Kimberley C. Zwiers, Claire de Wit, Ernst H. Beijk, Maria J. Ferraz, Marta Artola, Annemarie H. Meijer, Christian Tudorache, Daniela Salvatori, Rolf G. Boot, Johannes M. F. G. Aerts
Summary: In Gaucher disease, excessive GlcSph has little impact on (neuro)inflammation or GlcCer-laden macrophages, but rather seems harmful to th1-positive dopaminergic neurons.
JOURNAL OF LIPID RESEARCH
(2022)
Review
Cell Biology
Duarte C. Barral, Leopoldo Staiano, Claudia Guimas Almeida, Dan F. Cutler, Emily R. Eden, Clare E. Futter, Antony Galione, Andre R. A. Marques, Diego Luis Medina, Gennaro Napolitano, Carmine Settembre, Otilia V. Vieira, Johannes M. F. G. Aerts, Peace Atakpa-Adaji, Gemma Bruno, Antonella Capuozzo, Elvira De Leonibus, Chiara Di Malta, Cristina Escrevente, Alessandra Esposito, Paolo Grumati, Michael J. Hall, Rita O. Teodoro, Susana S. Lopes, J. Paul Luzio, Jlenia Monfregola, Sandro Montefusco, Frances M. Platt, Roman Polishchuck, Maria De Risi, Irene Sambri, Chiara Soldati, Miguel C. Seabra
Summary: This review presents current methods used to analyze lysosome morphology, positioning, motility, and function, discussing the strategies for identifying and assessing lysosome characteristics and functions. It aims to stimulate further research on lysosomes and encourage groundbreaking discoveries on this intriguing organelle that continues to surprise and excite cell biologists.
Article
Biochemistry & Molecular Biology
Rebecca E. Katzy, Maria J. Ferraz, Marc Hazeu, Hermen S. Overkleeft, Johannes M. F. G. Aerts
Summary: Glycosphingolipids (GSLs) play diverse roles in cells and abnormalities in their metabolism are associated with specific pathologies. Accurately measuring the in situ metabolism of GSLs and the modulatory impact of drugs is important for therapeutic purposes. In this study, the researchers developed a method using isotope-labelled precursors combined with liquid chromatography-mass spectrometry (MS)/MS analysis to monitor the de novo synthesis of glucosylceramide, which is a precursor of complex GSLs.
Article
Chemistry, Multidisciplinary
Ken Kok, Chi-Lin Kuo, Rebecca E. Katzy, Lindsey T. Lelieveld, Liang Wu, Veronique Roig-Zamboni, Gijsbert A. van der Marel, Jeroen D. C. Codee, Gerlind Sulzenbacher, Gideon J. Davies, Herman S. Overkleeft, Johannes M. F. G. Aerts, Marta Artola
Summary: This study reports a new class of reversible alpha-glucosidase inhibitors that mimic the conformation of the substrate, showing excellent enzyme inhibitory activity. These inhibitors possess selectivity towards specific glucosidases and demonstrate good stability and efficacy in cell and animal experiments, offering a promising alternative treatment for Pompe disease.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Correction
Biochemistry & Molecular Biology
Q. Su, S. P. Schroder, L. T. Lelieveld, M. J. Ferraz, M. Verhoek, R. G. Boot, H. S. Overkleeft, J. M. F. G. Aerts, M. Artola, C. -L. Kuo
Correction
Biochemistry & Molecular Biology
Qin Su, Sybrin P. Schroder, Lindsey T. Lelieveld, Maria J. Ferraz, Marri Verhoek, Rolf G. Boot, Herman S. Overkleeft, Johannes M. F. G. Aerts, Marta Artola, Chi-Lin Kuo
Review
Genetics & Heredity
A. Dardis, H. Michelakakis, P. Rozenfeld, K. Fumic, J. Wagner, E. Pavan, M. Fuller, S. Revel-Vilk, D. Hughes, T. Cox, J. Aerts, Int Working Grp Gaucher Dis IWGGD
Summary: This article provides an overview of Gaucher disease (GD) and discusses the challenges and gaps in GD diagnosis. To ensure timely and accurate diagnosis for patients with GD, evidence-based guidelines for the technical implementation and interpretation of biochemical and genetic testing have been developed. The guidelines aim to promote equitable access to GD diagnosis and standardize procedures.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Multidisciplinary Sciences
Marina Moraitou, Georgios Sotiroudis, Nikolaos Papagiannakis, Maria M. J. Ferraz, Aristotelis Xenakis, Johannes M. F. G. Aerts, Leonidas Stefanis, Helen Michelakakis
Summary: It is well established that patients with Gaucher disease, as well as carriers of the disease, have an increased risk for developing Parkinson's disease. The link between Gaucher disease and Parkinson's disease is the disturbed alpha-Synuclein homeostasis. In this study, alpha-Synuclein in red blood cell membranes was investigated in Gaucher disease patients, carriers, and patients undergoing Enzyme Replacement Therapy.
Article
Endocrinology & Metabolism
Eline C. B. Eskes, Martijn J. C. van der Lienden, Barbara Sjouke, Laura van Vliet, Marion M. M. G. Brands, Carla E. M. Hollak, Johannes M. F. G. Aerts
Summary: Plasma levels of GPNMB, a glycoprotein, were found to be elevated in ASMD patients and may serve as a potential biomarker for ASMD. GPNMB levels differed significantly between ASMD patients with mild to moderate visceral disease and those with severe visceral disease.
MOLECULAR GENETICS AND METABOLISM
(2023)
Article
Chemistry, Multidisciplinary
Daniel van der Gracht, Rhianna J. Rowland, Veronique Roig-Zamboni, Maria J. Ferraz, Max Louwerse, Paul P. Geurink, Johannes M. F. G. Aerts, Gerlind Sulzenbacher, Gideon J. Davies, Herman S. Overkleeft, Marta Artola
Summary: Lysosomal exoglycosidases are responsible for processing endocytosed glycans from the non-reducing end, and genetic mutations in these enzymes can cause lysosomal storage disorders. Developing effective therapeutic modalities to treat these diseases is a major objective in biomedicine. This study focuses on the development of screening assays to discover effective inhibitors for specific lysosomal glucosidases, with the aim of developing pharmacological chaperone therapeutics.
Meeting Abstract
Biotechnology & Applied Microbiology
Jolanda M. P. Liefhebber, Giso Brasser, Ilma Revers, Lieke Paerels, Maria J. Ferraz, Roelof Ottenhoff, Lukas K. Schwarz, Giorgia Squeri, Ines L. Pereira, Leonie Allart, Shrijana Tripathi, Nikoleta Efthymiopoulou, Greg Dobrynin, Paula S. Montenegro-Miranda, Carlie J. M. de Vries, Johannes M. F. G. Aerts, Ying Poi Liu