Article
Biochemistry & Molecular Biology
Xiaojing Zhou, Abdullah Md. Sheikh, Ken-ichi Matsumoto, Shingo Mitaki, Abu Zaffar Shibly, Yuchi Zhang, A. Garu, Shozo Yano, Atsushi Nagai
Summary: Through proteomic analysis of urine exosomes in AD model mice, we identified proteins related to lipid metabolism and A beta metabolism in the early stages of AD, providing new insights into the underlying pathological mechanism of early AD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Yasufumi Sakakibara, Yu Hirota, Kyoko Ibaraki, Kimi Takei, Sachie Chikamatsu, Yoko Tsubokawa, Takashi Saito, Takaomi C. Saido, Michiko Sekiya, Koichi M. Iijima
Summary: In aged App(NL-G-F/NL-G-F) knock-in mice, cortical A beta pathology induced significant reduction in the density of noradrenergic axons from the locus coeruleus, without neuron loss or tau pathology, suggesting a mechanism of noradrenergic neurodegeneration in Alzheimer's disease. Further investigation is needed to uncover the underlying mechanisms and develop effective therapeutics to halt AD progression.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Multidisciplinary Sciences
Daniel C. Ellwanger, Shoutang Wang, Simone Brioschi, Zhifei Shao, Lydia Green, Ryan Case, Daniel Yoo, Dawn Weishuhn, Palaniswami Rathanaswami, Jodi Bradley, Sara Rao, Diana Cha, Peng Luan, Shilpa Sambashivan, Susan Gilfillan, Samuel A. Hasson, Ian N. Foltz, Menno van Lookeren Campagne, Marco Colonna
Summary: TREM2 plays a critical role in microglia activation trajectories, with ligand engagement being essential for certain activation pathways. Activation trajectories induced by stimuli are more prominent in female mice than male mice. Injection of hT2AB can replenish depleted microglial pools lacking certain activation trajectories.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Pharmacology & Pharmacy
Marie Tautou, Sabiha Eddarkaoui, Florian Descamps, Paul-Emmanuel Larchanche, Jamal El Bakali, Liesel Mary Goveas, Melanie Dumoulin, Chloe Lamarre, David Blum, Luc Buee, Patricia Melnyk, Nicolas Sergeant
Summary: The study identified two molecules, MAGS02-14 and PEL24-199, with ss-secretase modulatory effects in cellulo. PEL24-199 was shown to restore short-term memory and reduce neurofibrillary degeneration, suggesting that lysosomotropic activity may not be essential for the effect on tau pathology.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yuki Kobayashi, Shogo Kohbuchi, Noriko Koganezawa, Yuko Sekino, Tomoaki Shirao, Takaomi C. Saido, Takashi Saito, Yumiko Saito
Summary: The primary cilium, a sensory organelle extending from cell bodies, plays a crucial role in neuronal integrity and connectivity. Research suggests a potential link between the structural alterations of neuronal cilia and the development of Alzheimer's disease and ciliopathies, which are characterized by memory and cognitive impairments.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Clinical Neurology
Shang Wang, Taiyang Zhu, Wanyan Ni, Chao Zhou, Hui Zhou, Li Lin, Yuting Hu, Xiaoyu Sun, Jingjing Han, Yan Zhou, Guoliang Jin, Jie Zu, Hongjuan Shi, Xingxing Yang, Zuohui Zhang, Fang Hua
Summary: This study investigates the role of early activation of Toll-like receptor 3 (TLR3) in the pathophysiological process of Alzheimer's disease (AD). The results showed that the early activation of TLR3 attenuated neuronal loss and neurobehavioral dysfunction in a mouse model of AD. This could be attributed to its role in A beta clearance, the inhibition of glial cells, and the regulation of neuroinflammation in the hippocampus.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Chemistry, Medicinal
Piya Temviriyanukul, Suwapat Kittibunchakul, Piyapat Trisonthi, Thanit Kunkeaw, Woorawee Inthachat, Dalad Siriwan, Uthaiwan Suttisansanee
Summary: This study found that tropical fruits have significant anti-Alzheimer's disease (AD) activity, particularly mango 'Namdokmai' which has the potential to prevent A beta (1-42)-mediated neurotoxicity and function as a BACE-1 inhibitor.
Article
Biochemistry & Molecular Biology
Liana Marengo, Fred Armbrust, Caroline Schoenherr, Steffen E. Storck, Ulrich Schmitt, Silvia Zampar, Oliver Wirths, Hermann Altmeppen, Markus Glatzel, Christoph Kaether, Sascha Weggen, Christoph Becker-Pauly, Claus U. Pietrzik
Summary: This study reports the generation of a transgenic mouse model of AD lacking the functional Mep1b gene (APP/lon x Mep1b(-/-)). The results showed that when meprin beta is absent, the levels of A beta 1-40 and 1-42 are reduced in APP/lon mice, and the deposition of N-terminally truncated A beta 2-x peptide is also decreased. Importantly, the loss of meprin beta improved cognitive abilities in APP/lon mice.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Cell Biology
Jasenka Rudan Njavro, Marija Vukicevic, Emma Fiorini, Lina Dinkel, Stephan A. Mueller, Anna Berghofer, Chiara Bordier, Stanislav Kozlov, Annett Halle, Katrin Buschmann, Anja Capell, Camilla Giudici, Michael Willem, Regina Feederle, Stefan F. Lichtenthaler, Chiara Babolin, Paolo Montanari, Andrea Pfeifer, Marie Kosco-Vilbois, Sabina Tahirovic
Summary: Amyloid-beta (A beta) deposition is a key factor in Alzheimer's disease (AD), and reductions in the phagocytic capacity of microglia, the brain immune cells, are associated with AD. ACI-24 vaccine targeting A beta effectively reduced AD pathology and induced an antibody response in a mouse model. The vaccine also decreased A beta plaque load and triggered microglial activation at A beta plaques while promoting a more ramified morphology of microglia distant from plaques.
Article
Neurosciences
Henrique Correia Campos, Deidiane Elisa Ribeiro, Debora Hashiguchi, Talita Glaser, Milena da Silva Milanis, Christiane Gimenes, Deborah Suchecki, Ricardo Mario Arida, Henning Ulrich, Beatriz Monteiro Longo
Summary: The aim of this study was to investigate the effects of resistance exercise on preventing and recovering from AD-related neuropathological conditions in APP/PS1 mice. The results showed that 4 weeks of resistance exercise improved locomotor activity and memory in APP/PS1 mice, and reduced A beta plaques and systemic inflammation. These findings suggest that resistance exercise plays a role in alleviating AD symptoms and can be an effective complementary treatment for AD.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Neurosciences
Victoria Gomez-Murcia, Kevin Carvalho, Bryan Thiroux, Raphaelle Caillierez, Melanie Besegher, Nicolas Sergeant, Luc Buee, Emile Faivre, David Blum
Summary: Due to the complexity of Alzheimer's disease, it is of interest to find multitarget approaches that can mitigate multiple pathogenic mechanisms. In this study, the potential of Doxycycline (Dox), a second-generation tetracycline, in the APP/PS1 mouse model of amyloidogenesis was evaluated. The results showed that Dox moderately improved spatial memory in APP/PS1 mice without major effect on amyloid lesions. The study also found that Dox enhanced the amyloid-dependent upregulation of neuroinflammatory markers. Overall, chronic Dox delivery did not provide significant pathophysiological improvements in the APP/PS1 mouse model.
Article
Biochemistry & Molecular Biology
Laura Schnoeder, Wenqiang Quan, Ye Yu, Inge Tomic, Qinghua Luo, Wenlin Hao, Guoping Peng, Dong Li, Klaus Fassbender, Yang Liu
Summary: In the brains of Alzheimer's disease (AD) mice, deficiency of IKK beta in neurons reduces levels of amyloid-beta-peptide (Aβ) and phosphorylated tau (p-tau), modifies inflammatory activation, and improves cognitive function. The deficiency also decreases BACE1 protein and activity, increases expression of PP2A isoform A, and enhances autophagy. However, the protective effects of IKK beta deficiency differ in APP and tau-transgenic mice. Further studies are needed to understand the interaction between Aβ and p-tau before targeting IKK beta/NF-kappa B for AD therapies.
Article
Cell Biology
Luming Zhuang, Chenglin Li, Fei Peng, Elleen Xue, Wenzhe Li, Xinyue Sun, Ping Chen, Qian Zhou, Lei Xue
Summary: Through studying fly AD models, it was found that inhibiting ESCRT components can improve AD-like symptoms induced by APP, suggesting the important role of ESCRT in AD pathogenesis and providing clues for alternative therapeutic strategies for AD.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shiveena Bhatia, Manjinder Singh, Pratibha Sharma, Somdutt Mujwar, Varinder Singh, Krishna Kumar Mishra, Thakur Gurjeet Singh, Tanveer Singh, Sheikh Fayaz Ahmad
Summary: Alzheimer's disease, the leading cause of dementia, is characterized by the deposition of plaques and tangles in the brain, leading to cell degeneration. Researchers are developing BACE-1 enzyme inhibitors to prevent plaque buildup. In this study, Elenbecestat analogues were analyzed using structure-based drug design and scaffold morphing, and SB306 and SB12 were found to interact well with the catalytic dyad motifs of the enzyme, showing drug-like properties and high thermodynamic stability.
Article
Neurosciences
Christian Ulrich von Linstow, Jonas Waider, Marianne Skov-Skov Bergh, Marco Anzalone, Cecilie Madsen, Aina Battle Nicolau, Martin Wirenfeldt, Klaus-Peter Lesch, Bente Finsen
Summary: This study investigates the impact of targeted inactivation of Tph2 on amyloidosis in transgenic mice. The results suggest that Tph2 inactivation does not affect the levels of A beta, but it does influence the processing of A beta PP. Additionally, 5-HT may play a protective role in the viability of APP/PS1 mice.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Veterinary Sciences
Nora Denk, Claudia Senn, Bjoern Jacobsen, Tobias Schnitzer
LABORATORY ANIMALS
(2018)
Article
Medicine, Research & Experimental
Laurence A. Hutton-Smith, Eamonn A. Gaffney, Helen M. Byrne, Antonello Caruso, Philip K. Maini, Norman A. Mazer
MOLECULAR PHARMACEUTICS
(2018)
Article
Chemistry, Medicinal
Hasane Ratni, Martin Ebeling, John Baird, Stefanie Bendels, Johan Bylund, Karen S. Chen, Nora Denk, Zhihua Feng, Luke Green, Melanie Guerard, Philippe Jablonski, Bjoern Jacobsen, Omar Khwaja, Heidemarie Kletzl, Chien-Ping Ko, Stefan Kustermann, Anne Marquet, Friedrich Metzger, Barbara Mueller, Nikolai A. Naryshkin, Sergey V. Paushkin, Emmanuel Pinard, Agnes Poirier, Michael Reutlinger, Marla Weetall, Andreas Zeller, Xin Zhao, Lutz Mueller
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Pathology
Bjorn Jacobsen, Christian Freichel, Anne Eichinger-Chapelon, Andreas Brink, Jean-Christophe Hoflack, Mudher Albassam, Barbara Lenz
TOXICOLOGIC PATHOLOGY
(2019)
Article
Pathology
Keith Jones, Joanna Harding, Andy Makin, Pramila Singh, Bjoern Jacobsen, Lars Friis Mikkelsen
TOXICOLOGIC PATHOLOGY
(2019)
Article
Medicine, Research & Experimental
Antonello Caruso, Matthias Futh, Ruben Alvarez-Sanchez, Sara Belli, Cheikh Diack, Katie F. Maass, Dietmar Schwab, Hubert Kettenberger, Norman A. Mazer
MOLECULAR PHARMACEUTICS
(2020)
Article
Biochemical Research Methods
Antonello Caruso, Jannik Vollmer, Matthias Machacek, Elod Kortvely
PLOS COMPUTATIONAL BIOLOGY
(2020)
Article
Pharmacology & Pharmacy
Simon Hauri, Paulina Jakubiak, Matthias Fueth, Stefan Dengl, Sara Belli, Ruben Alvarez-Sanchez, Antonello Caruso
Review
Pathology
Mikala Skydsgaard, Zuhal Dincer, Wanda M. Haschek, Kris Helke, Binod Jacob, Bjoern Jacobsen, Gitte Jeppesen, Atsuhiko Kato, Hiroaki Kawaguchi, Sean McKeag, Keith Nelson, Susanne Rittinghausen, Dirk Schaudien, Vimala Vemireddi, Zbigniew W. Wojcinski
Summary: The INHAND Project aims to develop an internationally accepted nomenclature for lesions in laboratory animals, providing standardized names for microscopic lesions observed in various tissues and organs, supported by color photomicrographs and an electronic database. This initiative will promote a common language among regulatory and scientific research organizations globally, enhancing international exchanges of information among toxicologists and pathologists.
TOXICOLOGIC PATHOLOGY
(2021)
Article
Clinical Neurology
Robert C. Sergott, Giulia M. Amorelli, Giovanni Baranello, Emmanuel Barreau, Shannon Beres, Steven Kane, Eugenio Mercuri, Lorenzo Orazi, Melissa SantaMaria, Gemma Tremolada, Diletta Santarsiero, Agnieszka Waskowska, Shigeko Yashiro, Nora Denk, Sabine Furst-Recktenwald, Marianne Gerber, Ksenija Gorni, Birgit Jaber, Bjoern Jacobsen, Lutz Mueller, Stephane Nave, Renata S. Scalco, Stefania B. Marzoli
Summary: Evaluation of ophthalmologic safety in patients with spinal muscular atrophy (SMA) treated with risdiplam showed no retinal structural or functional changes, suggesting that safety ophthalmologic monitoring is not needed in these patients.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Article
Chemistry, Medicinal
Marianne K. Vormann, Jelle Vriend, Henriette L. Lanz, Linda Gijzen, Angelique van den Heuvel, Simon Hutter, Jos Joore, Sebastiaan J. Trietsch, Christiaan Stuut, Tom T. G. Nieskens, Janny G. P. Peters, Daniela Ramp, Michaela Caj, Frans G. M. Russel, Bjoern Jacobsen, Adrian Roth, Shuyan Lu, Joseph W. Polli, Anita A. Naidoo, Paul Vulto, Rosalinde Masereeuw, Martijn J. Wilmer, Laura Suter-Dick
Summary: The Nephroscreen platform, using a combination of cell viability, LDH, and miRNA release, proved to be a robust and predictive method for detecting drug-induced kidney injury. It is compatible with automated pipetting, suitable for long-term experiments, and offers a valuable tool for replacing animal testing and supporting the 3Rs principles.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Medicine, Research & Experimental
Paulina Jakubiak, Ruben Alvarez-Sanche, Matthias Fueth, Olaf Broders, Hubert Kettenberger, Kay Stubenrauch, Antonello Caruso
Summary: This study on ocular pharmacokinetics in macaques examined the durability of different anti-VEGF protein formats. The results indicated the translational significance of cynomolgus monkeys as animal models for ocular research, and highlighted molecular size as a determinant of ocular drug disposition.
MOLECULAR PHARMACEUTICS
(2021)
Article
Medicine, Legal
Rostam Namdari, Keith Jones, Samuel S. Chuang, Steven Van Cruchten, Zuhal Dincer, Noel Downes, Lars Friis Mikkelsen, Joanna Harding, Sven Jaeckel, Bjoern Jacobsen, Jacqueline Kinyamu-Akunda, Andreanne Lortie, Sofiene Mhedhbi, Susanne Mohr, Michael W. Schmitt, Helen Prior
Summary: Nonclinical safety assessment is essential in drug development, and selecting the appropriate animal species for toxicity testing is crucial for identifying potential effects in humans. Different companies have developed decision processes tailored to their molecules, experience, and 3Rs policies, focusing on metabolic similarity and pharmacological activity for NCEs, and target epitope presence for biologics.
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2021)
Article
Toxicology
Jelle Vriend, Marianne K. Vormann, Henriette L. Lanz, Jos Joore, Sebastiaan J. Trietsch, Frans G. M. Russel, Bjoern Jacobsen, Adrian Roth, Shuyan Lu, Joseph W. Polli, Anita A. Naidoo, Rosalinde Masereeuw, Martijn J. Wilmer, Laura Suter-Dick
Summary: Proximal tubule epithelial cells play a key role in renal drug transport and secretion, making them vulnerable to drug-induced kidney injury. Nephroscreen, a high-throughput, three-dimensional microfluidic platform, is an effective tool for detecting drug-induced nephrotoxicity. Nephroscreen allows for a variety of read-outs, is compatible with automated pipetting, and can be used for long-term experiments.
CURRENT OPINION IN TOXICOLOGY
(2021)
Article
Oncology
Isabelle Solomon, Maria Amann, Anne Goubier, Frederick Arce Vargas, Dimitrios Zervas, Chen Qing, Jake Y. Henry, Ehsan Ghorani, Ayse U. Akarca, Teresa Marafioti, Anna sledzinska, Mariana Werner Sunderland, Dafne Franz Demane, Joanne Ruth Clancy, Andrew Georgiou, Josephine Salimu, Pascal Merchiers, Mark Adrian Brown, Reto Flury, Jan Eckmann, Claudio Murgia, Johannes Sam, Bjoern Jacobsen, Estelle Marrer-Berger, Christophe Boetsch, Sara Belli, Lea Leibrock, Joerg Benz, Hans Koll, Roger Sutmuller, Karl S. Peggs, Sergio A. Quezada