Article
Biochemistry & Molecular Biology
Shofiul Azam, Md. Ezazul Haque, Duk-Yeon Cho, Joon-Soo Kim, Md. Jakaria, In-Su Kim, Dong-Kug Choi
Summary: Dioscin treatment can protect neuronal cells by inducing autophagy and suppressing the mitochondrial apoptosis pathway, reducing apoptosis and autophagic flux impairment caused by MPP+.
Article
Neurosciences
Belinda Fouche, Stephanie Turner, Rebecca Gorham, Eloise J. Stephenson, Simon Gutbier, Joanna L. Elson, Olimpo Garcia-Beltran, Francois H. van der Westhuizen, Ilse S. Pienaar
Summary: This study demonstrates the neuroprotective potential of a new polyhydroxyl coumarin, CT51, against the mitochondrial toxin MPP+. CT51 preserves neural function and circuitry against PD-related damage by targeting cell bodies and axons, restoring somatic cell viability and neurite processes. Additionally, CT51 acts as an antioxidant agent and downregulates the expression of HIF-1 alpha, providing further protection against oxidative stress.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Cell Biology
Bhupesh Vaidya, Mahesh Polepalli, Shyam Sunder Sharma, Jitendra Narain Singh
Summary: Mitochondrial dysfunction is closely associated with neurodegenerative disorders like Parkinson's disease. 2-APB has shown promise in targeting mitochondrial dysfunctions and improving the pathological conditions of Parkinson's disease.
Review
Cell Biology
Samir Kumar Beura, Abhishek Ramachandra Panigrahi, Pooja Yadav, Sunil Kumar Singh
Summary: Parkinson's disease is a common neurodegenerative disease characterized by motor and non-motor dysfunctions. Platelets play an important role in Parkinson's disease and may be a target for treatment.
AGEING RESEARCH REVIEWS
(2022)
Article
Biotechnology & Applied Microbiology
Chuo Li, Yusheng Zhang, Rongrong Liu, Yuzhen Mai
Summary: The study demonstrated that Ramelteon could increase cell viability, reduce oxidative stress, and mitigate MPP+-induced neurotoxicity through a mitochondrial-dependent pathway.
Review
Biochemistry & Molecular Biology
Chi-Jing Choong, Hideki Mochizuki, Cesar Borlongan
Summary: Mitochondrial dysregulation is strongly associated with the pathogenesis of Parkinson's disease (PD), with mutated genes affecting mitochondrial features. Disruption of mitochondrial quality control and abnormal secretion of mitochondrial contents play a role in PD, and circulating mitochondrial DNAs can elicit inflammatory response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Qiang Li, Peilan Zhang, Yun Cai
Summary: Genkwanin attenuated neuroinflammation and neurotoxicity by inhibiting TLR4/MyD88/NLRP3 inflammasome pathway in MPP+-induced cellular model of PD.
Article
Pharmacology & Pharmacy
M. E. Arslan, A. Yilmaz
Summary: This study investigated the neuroprotective effects of Geranium robertianum leaf extract in a Parkinson's disease model. The results showed that the extract ameliorated cytotoxicity and oxidative damage caused by MPP+ and exhibited a protective activity against MPP+-induced apoptosis. Therefore, Geranium robertianum could be a promising candidate for the treatment of Parkinson's disease through its neuroprotective mechanisms.
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Sunil Bhurtel, Eugene Bok, Nikita Katila, Jaekwang Kim, Dong-Young Choi
Summary: The study demonstrated that methylene blue protects neurons from MPP+-induced toxicity by activating the antioxidant system and reducing oxidative stress and mitochondrial impairment.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Di Hu, Zunren Liu, Xin Qi
Summary: This study found that activation of UPRmt can reduce mitochondrial reactive oxygen species (ROS) production and improve cell survival in MPP+-treated cells. Overexpression of specific transcription factor 5 can protect cells from MPP+-induced oxidative stress and cell death.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Neurosciences
Akhil Sharma, Viktoriia Bazylianska, Anna Moszczynska
Summary: PKO rats display a certain resistance to METH neurotoxicity, possibly mediated by lowered DA levels and downregulated mitochondria.
EXPERIMENTAL NEUROLOGY
(2021)
Review
Clinical Neurology
Kaitlyn M. L. Cramb, Dayne Beccano-Kelly, Stephanie J. Cragg, Richard Wade-Martins
Summary: Cramb et al. provide a review of evidence suggesting dopamine release deficits occur prior to neurodegeneration in Parkinson's disease. They also highlight the need for further investigation in understanding the mechanisms behind these deficits.
Article
Toxicology
Sierra L. Boyd, Nathan C. Kuhn, Joseph R. Patterson, Anna C. Stoll, Sydney A. Zimmerman, Mason R. Kolanowski, Joseph J. Neubecker, Kelvin C. Luk, Eric S. Ramsson, Caryl E. Sortwell, Alison Bernstein
Summary: Parkinson's disease (PD) is the fastest-growing neurological disease worldwide, suggesting a role of environmental factors. Studies have shown that persistent organic pollutants, including the organochlorine pesticide dieldrin, increase PD risk. In mice, developmental dieldrin exposure exacerbates neuronal susceptibility to MPTP and synucleinopathy.
TOXICOLOGICAL SCIENCES
(2023)
Article
Biology
Tom Leah, Irina Vazquez-Villasenor, Laura Ferraiuolo, Stephen B. Wharton, Heather Mortiboys
Summary: Various cell models, such as primary patient derived cells, SHSY-5Y cells and in vivo models, have been extensively utilized to study the contribution of mitochondrial dysfunction in Parkinson's disease.
Article
Biochemistry & Molecular Biology
Moises Rubio-Osornio, Carmen T. Gomez-De Leon, Sergio Montes, Carmen Rubio, Camilo Rios, Antonio Monroy, Jorge Morales-Montor
Summary: Parkinson's disease is characterized by oxidative stress and immune activation. Simvastatin, a cholesterol-regulating drug, can protect against atherosclerosis disease. Pretreatment with simvastatin reduced MPP+-induced damage in rats and decreased inflammation response proteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Toxicology
Cleo Tebby, Wang Gao, Johannes Delp, Giada Carta, Wanda van der Stel, Marcel Leist, Paul Jennings, Bob van de Water, Frederic Y. Bois
Summary: This study used quantitative Adverse Outcome Pathways (qAOPs) and mathematical models to calibrate the mitochondrial toxicity of two chemicals in different cell lines. The results showed that there were practical difficulties in calibrating qAOPs in different cell types, and even when the same key event readouts were measured, the mathematical functions used may not be the same. Cross-validation also revealed underestimation of toxicity in LHUMES cells.
TOXICOLOGY IN VITRO
(2022)
Article
Food Science & Technology
Jan G. Hengstler, Matthias Baum, Alexander T. Cartus, Patrick Diel, Gerhard Eisenbrand, Karl-Heinz Engel, Barbara Engeli, Bernd Epe, Tilman Grune, Sabine Guth, Dirk Haller, Volker Heinz, Michael Hellwig, Thomas Henle, Hans-Ulrich Humpf, Henry Jaeger, Hans-Georg Joost, Sabine E. Kulling, Dirk W. Lachenmeier, Alfonso Lampen, Marcel Leist, Angela Mally, Doris Marko, Ute Noethlings, Elke Roehrdanz, Angelika Roth, Joachim Spranger, Richard Stadler, Pablo Steinberg, Stefan Vieths, Wim Waetjen
Summary: Acetaldehyde is naturally present in many foods and used as a flavoring agent. However, there is uncertainty regarding its carcinogenicity and genotoxic potential after oral exposure. Due to incomplete data and concerns about its genotoxicity, a science-based health risk assessment for the use of acetaldehyde as a flavoring agent is not currently possible. Therefore, a re-evaluation of the use of acetaldehyde as a food additive is recommended for precautionary consumer protection.
JOURNAL OF CONSUMER PROTECTION AND FOOD SAFETY
(2022)
Article
Environmental Sciences
Jonathan Blum, Stefan Masjosthusmann, Kristina Bartmann, Farina Bendt, Xenia Dolde, Arif Doenmez, Nils Foerster, Anna-Katharina Holzer, Ulrike Huebenthal, Hagen Eike Kessel, Sadiye Kilic, Joerdis Klose, Melanie Pahl, Lynn-Christin Stuerzl, Iris Mangas, Andrea Terron, Kevin M. Crofton, Martin Scholze, Axel Mosig, Marcel Leist, Ellen Fritsche
Summary: Developmental neurotoxicity is a major safety concern for chemicals, but animal studies provide limited data. Higher throughput test methods with improved human relevance are urgently needed. This study explores the feasibility of using new approach methods for developmental neurotoxicity hazard assessment.
Article
Toxicology
Liliana Capinha, Yaran Zhang, Anna-Katharina Holzer, Anna-Katharina Uckert, Melinda Zana, Giada Carta, Cormac Murphy, Jenna Baldovini, Zahra Mazidi, Johannes Grillari, Andras Dinnyes, Bob van de Water, Marcel Leist, Jan N. M. Commandeur, Paul Jennings
Summary: This study used six human derived cell models to investigate the effects of trichloroethylene (TCE) S-conjugates. The results showed that TCE S-conjugates induced Nrf2 pathway and unfolded protein response, which may explain the nephrotoxicity and neurotoxicity of TCE. This study expands our knowledge on the tissue specificity of TCE S-conjugates and highlights the value of human cell models and transcriptomics in mechanistic studies.
ARCHIVES OF TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Petra Kranaster, Jonathan Blum, Jeremias E. G. A. Dold, Valentin Wittmann, Marcel Leist
Summary: Metabolic glycoengineering (MGE) is a method for visualizing carbohydrates on live cells. It allows the fluorescent labeling of sialic acid (Sia) sugar residues on neuronal plasma membranes. By using human dopaminergic neurons as a model system, this study developed a method for differential labeling of sialylated membrane lipids or sialylated N-glycosylated proteins on live neurons.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Ilinca Suciu, Johannes Delp, Simon Gutbier, Anna-Katharina Ueckert, Anna-Sophie Spreng, Philipp Eberhard, Christiaan Karreman, Falk Schreiber, Katrin Madjar, Joerg Rahnenfuehrer, Ivana Celardo, Ivano Amelio, Marcel Leist
Summary: Proteasome inhibition is related to parkinsonian pathology and dopaminergic neuron degeneration. In this study, the metabolome and transcriptome regulations of human LUHMES neurons exposed to MG-132 were investigated, revealing compromised energy metabolism and activation of stress response pathways. These findings provide insights into the cellular responses to proteasome dysfunction and potential therapeutic interventions for Parkinson's disease.
Article
Cell Biology
Giada Carta, Wanda van der Stel, Emma W. J. Scuric, Liliana Capinha, Johannes Delp, Susanne Hougaard Bennekou, Anna Forsby, Paul Walker, Marcel Leist, Bob van de Water, Paul Jennings
Summary: Analysis of transcriptomic alterations upon chemical challenge reveals specific pathway activation and transcriptional modulations, providing mechanistic information on the toxic mode of action of chemical compounds. In this study, the transcriptional landscape of mitochondrial impairment caused by inhibition of the electron transport chain was assessed in human renal cells. The unfolded protein response pathway, particularly the PERK/ATF4 branch, was identified as a common cellular response to ETC inhibitions, which could help identify mitochondrial liabilities of chemicals in both legacy data and prospective studies.
CELL BIOLOGY AND TOXICOLOGY
(2023)
Review
Food Science & Technology
Sabine Guth, Matthias Baum, Alexander T. Cartus, Patrick Diel, Karl-Heinz Engel, Barbara Engeli, Bernd Epe, Tilman Grune, Dirk Haller, Volker Heinz, Michael Hellwig, Jan G. Hengstler, Thomas Henle, Hans-Ulrich Humpf, Henry Jaeger, Hans-Georg Joost, Sabine E. Kulling, Dirk W. Lachenmeier, Alfonso Lampen, Marcel Leist, Angela Mally, Doris Marko, Ute Noethlings, Elke Roehrdanz, Angelika Roth, Joachim Spranger, Richard Stadler, Pablo Steinberg, Stefan Vieths, Wim Waetjen, Gerhard Eisenbrand
Summary: This opinion from the SKLM presents arguments for an updated risk assessment of acrylamide (AA) exposure in diet, based on a critical review of relevant scientific evidence. The SKLM concludes that as long as exposure limits for AA are not exceeded, genotoxic effects leading to carcinogenicity are unlikely to occur. Considering the totality of evidence, the SKLM deems it scientifically justified to establish a tolerable daily intake (TDI) as a health-based guidance value.
FOOD AND CHEMICAL TOXICOLOGY
(2023)
Article
Toxicology
Philip Botham, Mark T. D. Cronin, Richard Currie, John Doe, Dorothee Funk-Weyer, Timothy W. Gant, Marcel Leist, Sue Marty, Bennard van Ravenzwaay, Carl Westmoreland
Summary: The REACH regulation determines the studies that must be conducted based on the annual tonnage of chemicals manufactured or imported into the EU. However, this criterion does not consider the physico-chemical properties and use patterns that determine exposure. An analysis of the REACH mandated study lists reveals that only 19% of registered substances have datasets covering all areas of health concern. Limited information is available for areas such as repeat and extended exposure and carcinogenicity. Using New Approach Methodologies (NAMs) at lower tonnage bands could provide additional information and enhance the use of NAMs by registrants and regulators. Projects in Europe are currently developing NAM-based assessment frameworks that could be used for low tonnage chemicals once confidence has been gained through evaluation with data-rich chemicals.
ARCHIVES OF TOXICOLOGY
(2023)
Editorial Material
Medicine, Research & Experimental
Alessio Butera, Lena Smirnova, Elisa Ferrando-May, Thomas Hartung, Thomas Brunner, Marcel Leist, Ivano Amelio
Summary: Human health is influenced by both genetics and environment. Different responses can be observed in groups of individuals exposed to the same environmental factors. The concept of gene-environment interactions is still not well defined, but examples of these interactions driving disease development are provided in this article. The cellular epigenome is suggested to hold the key to unravel these complex layers of regulation. Developing a method to decode epigenetic information could provide quantitative measures of disease risk, similar to the concept of an epigenetic clock for estimating biological age.
EMBO MOLECULAR MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Karin Grillberger, Eike Collen, Claudia Immacolata Trivisani, Jonathan Blum, Marcel Leist, Gerhard F. Ecker
Summary: Toxic effects of neonicotinoids and their metabolites on human neurons were investigated using a combination of in silico and in vitro methods. Calcium imaging on neurons confirmed a key event predicted by molecular simulations, providing a new approach for next-generation risk assessments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Anna Cherianidou, Franziska Kappenberg, Florian Seidel, Aviseka Acharya, Panagiota Papazoglou, Sureshkumar Perumal Srinivasan, Juergen Hescheler, Luying Peng, Marcel Leist, Jan G. Hengstler, Joerg Rahnenfuehrer, Agapios Sachinidis
Summary: Animal studies for embryotoxicity evaluation are limited in their relevance to humans due to species differences. This study used human induced pluripotent stem cells (hiPSCs) to recapitulate cardiomyogenesis and identify key genes and processes affected by potential teratogens. We found that certain retinoids completely blocked cardiomyogenesis in hiPSCs and established a Developmental Cardiotoxicity Index that accurately differentiates teratogens from non-teratogens.
CELL DEATH DISCOVERY
(2023)
Review
Medicine, Research & Experimental
Winfried Neuhaus, Birgit Reininger-Gutmann, Beate Rinner, Roberto Plasenzotti, Doris Wilflingseder, Joery De Kock, Tamara Vanhaecke, Vera Rogiers, Dagmar Jirova, Kristina Kejlova, Lisbeth E. Knudsen, Rasmus Normann Nielsen, Burkhard Kleuser, Vivian Kral, Christa Thoene-Reineke, Thomas Hartung, Giorgia Pallocca, Costanza Rovida, Marcel Leist, Stefan Hippenstiel, Annemarie Lang, Ida Retter, Stephanie Kraemer, Peter Jedlicka, Katharina Ameli, Ellen Fritsche, Julia Tigges, Eliska Kuchovska, Manuela Buettner, Andre Bleich, Nadine Baumgart, Jan Baumgart, Marcus W. Meinhardt, Rainer Spanagel, Sabine Chourbaji, Bettina Kraenzlin, Bettina Seeger, Maren von Koeckritz-Blickwede, Jose M. Sanchez-Morgado, Viola Galligioni, Daniel Ruiz-Perez, Dania Movia, Adriele Prina-Mello, Arti Ahluwalia, Valeria Chiono, Arno C. Gutleb, Marthe Schmit, Bea van Golen, Leane van Weereld, Anne Kienhuis, Erica van Oort, Jan van der Valk, Adrian Smith, Joanna Roszak, Maciej Stepnik, Zuzanna Sobanska, Edyta Reszka, I. Anna S. Olsson, Nuno Henrique Franco, Bogdan Sevastre, Helena Kandarova, Sara Capdevila, Jessica Johansson, Emma Svensk, Christopher R. Cederroth, Jenny Sandstroem, Ian Ragan, Nataliia Bubalo, Jens Kurreck, Horst Spielmann
Summary: Three Rs centres and platforms are dedicated to the Replacement, Reduction and Refinement of animal use in experiments. They play a crucial role in promoting the implementation of Directive 2010/63/EU and disseminating information.
ATLA-ALTERNATIVES TO LABORATORY ANIMALS
(2022)
Article
Medicine, Research & Experimental
Manuela Cassotta, Hugo Geerts, Lise Harbom, Tiago F. Outeiro, Iosif Pediaditakis, Orly Reiner, Stefan Schildknecht, Jens C. Schwamborn, Jarrod Bailey, Kathrin Herrmann, Helena T. Hogberg
Summary: Parkinson's disease (PD) is a complex neurodegenerative condition with a lack of preventive or curative therapies. New approach methodologies (NAMs) hold potential to advance PD research and reduce the reliance on animal-based studies. Key recommendations to advance PD research include integrating NAMs, learning from other neurodegenerative diseases, increasing data sharing, promoting innovative pilot studies, and accessing philanthropic funding.
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
(2022)
Article
Medicine, Research & Experimental
Giorgia Pallocca, Martijn J. Mone, Hennicke Kamp, Mirjam Luijten, Bob van de Water, Marcel Leist
Summary: In many industrial sectors, there is a need for reliable methods to evaluate the safety of chemicals based on human biology and pathology. To address this need, animal-free new approach methods (NAMs) have been developed and implemented in risk assessment. The RISK-HUNT3R project aims to combine computational toxicology, in vitro toxicology, and systems biology to create a comprehensive next-generation risk assessment strategy. This strategy is expected to result in faster and more accurate risk assessment procedures.
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
(2022)