Article
Biochemistry & Molecular Biology
Shikha Grover, Thao Pham, Anna Jones, Cristina Sinobas-Pereira, Marina Villoch Diaz Maurino, Evan C. C. Garrad, Nyasha J. J. Makoni, Antanisha Parks, Ryan J. J. Domalewski, Gabriel Riggio, Hannah An, Kunhua Chen, Michael R. R. Nichols
Summary: This study developed and characterized a new class of monoclonal antibodies (mAbSL) that selectively target A beta protofibrils, inhibiting A beta monomer aggregation and altering its dynamics.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Clinical Neurology
Shobha Dhadda, Michio Kanekiyo, David Li, Chad J. Swanson, Michael Irizarry, Scott Berry, Lynn D. Kramer, Donald A. Berry
Summary: The sensitivity analysis demonstrates that Lecanemab shows positive effects in treating Alzheimer's disease across different statistical methods, endpoints, and over time.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Review
Chemistry, Multidisciplinary
John H. Viles
Summary: The accumulation of amyloid-beta peptides (Aβ) is crucial in Alzheimer's disease development. The interaction between various Aβ assemblies and lipid membranes or membrane receptors result in increased membrane permeability and cellular homeostasis disruption, which plays a key role in the pathology of Alzheimer's disease. Aβ can affect lipid membranes in multiple ways, including a carpeting effect, a detergent effect, and the formation of Aβ ion-channel pores. Recent advancements in imaging techniques have improved our understanding of Aβ-induced membrane disruption. Understanding the relationship between different Aβ structures and membrane permeability will guide the development of therapeutics targeting Aβ cytotoxicity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Immunology
James S. Foster, Manasi Balachandran, Trevor J. Hancock, Emily B. Martin, Sallie Macy, Craig Wooliver, Tina Richey, Alan Stuckey, Angela D. Williams, Joseph W. Jackson, Stephen J. Kennel, Jonathan S. Wall
Summary: Systemic amyloidosis is a progressive disorder characterized by the deposition of amyloid fibrils and accessory proteins in organs and tissues. Current treatment focuses on reducing amyloid production, but this study introduces a peptide-antibody fusion molecule (mIgp5) that enhances macrophage uptake of amyloid, potentially offering a new approach for treating the disease.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Lanlan Yu, Ruonan Wang, Shucong Li, Ufuoma I. Kara, Eric C. Boerner, Boyuan Chen, Feiyi Zhang, Zhongyi Jian, Shuyuan Li, Mingwei Liu, Yang Wang, Shuli Liu, Yanlian Yang, Chen Wang, Wenbo Zhang, Yuxing Yao, Xiaoguang Wang, Chenxuan Wang
Summary: Scanning tunneling microscopy (STM) is used to distinguish 18 coexisting conformational substates of the β-strand of hIAPP 8-37 and analyze the peptide-peptide interactions. This method also validates the existence of multiple conformations in other β-sheet peptide assemblies. The results provide insights into the conformational ensemble and interpeptide interactions in β-sheet peptide assembly.
ACS CENTRAL SCIENCE
(2023)
Article
Polymer Science
Carlos Noble Jesus, Rhys Evans, Joe Forth, Carolina Estarellas, Francesco Luigi Gervasio, Giuseppe Battaglia
Summary: The study presents the design, simulation, synthesis, and reversible self-assembly of nanofibrils using polyhistidine-based oligopeptides. The inclusion of aromatic amino acids in the histidine block leads to the formation of amyloid-like fibrils with distinct antiparallel beta-strands. The structures undergo self-assembly in response to pH changes, offering potential for biotechnological and biomedical applications with pH-responsive fibrils in a physiologically relevant range.
Review
Virology
Wesley R. Naeimi, Tricia R. Serio
Summary: The formation of amyloid fibers is associated with various diseases and phenotypic conditions, and they can assemble into multi-protofibril and high-order architectures. Using prion propagation in yeast as a model, researchers can explore the connection between these aggregation states and the biological consequences of amyloid dynamics.
Article
Pharmacology & Pharmacy
Grace E. Vitek, Boris Decourt, Marwan N. Sabbagh
Summary: Nearly a dozen mAbs have been developed for the treatment of AD, and newer mAbs such as lecanemab target more specific Aβ types. Data from phase 2 trials suggest promising efficacy and manageable risk of ARIAs. Lecanemab is currently being studied in phase 3 trials.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2023)
Article
Chemistry, Multidisciplinary
Qiantao Song, Yi Li, Zhicheng Jin, Hai Liu, Matthew N. Creyer, Wonjun Yim, Yanping Huang, Xiaobing Hu, Tengyu He, Yajuan Li, Shana O. Kelley, Lingyan Shi, Jiajing Zhou, Jesse V. Jokerst
Summary: This study reports the mild and unique formation of luminescent spherulites at room temperature using benzene-1,4-dithiol. These spherulites not only exhibit robust structure but also show broad clusterization-triggered emission. They also demonstrate biocompatibility and efficient cellular uptake, making them valuable as traceable drug carriers.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemical Research Methods
Mantas Ziaunys, Kamile Mikalauskaite, Andrius Sakalauskas, Vytautas Smirnovas
Summary: The aggregation of amyloidogenic proteins is related to various diseases, with limited treatment options currently available. The challenge in the discovery of potential anti-amyloid molecules lies in identifying the actual inhibitors from complex mixtures. This study successfully scavenged potential aggregation-inhibiting molecules from different compounds and effectively separated them from the aggregates.
BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Tongtong Hou, Nan Zhang, Chaoren Yan, Minling Ding, Huizhe Niu, Ping Guan, Xiaoling Hu
Summary: This study developed a curcumin lysozyme-imprinted nanosphere (CUR-MIMS) that effectively inhibited the aggregation of lysozyme and showed good biocompatibility, demonstrating its potential as a therapeutic platform for amyloidosis.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Geriatrics & Gerontology
Francesca Mantile, Angelo Capasso, Nadia Villacampa, Maria Donnini, Giovanna L. Liguori, Gabriela Constantin, Piergiuseppe De Berardinis, Michael T. Heneka, Antonella Prisco
Summary: Immunization against Aβ is being explored for AD prevention, but current vaccines face challenges in safety and immunogenicity. While immunization with (1-11)E2 can induce antibody response, it does not protect against Aβ accumulation and neuroinflammation, highlighting the need for further research into the immune response against Aβ that could prevent accumulation.
AGING CLINICAL AND EXPERIMENTAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Mantas Ziaunys, Andrius Sakalauskas, Tomas Sneideris, Vytautas Smirnovas
Summary: Protein aggregation into amyloid fibrils is associated with various disorders, but the mechanisms behind the conversion of non-harmful proteins into such aggregates are not fully understood. Recent studies suggest that multiple types of protein aggregates may co-exist in tissues of patients with amyloid-related disorders, potentially influencing each other.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Jozef Adamcik, Francesco Simone Ruggeri, Joshua T. Berryman, Afang Zhang, Tuomas P. J. Knowles, Raffaele Mezzenga
Summary: The nanomechanical properties and structural transitions of amyloid fibrils and microcrystals can be unraveled at the single aggregate scale using single molecule nanomechanical mapping and infrared nanospectroscopy techniques. Different morphologies of amyloid aggregates exhibit varying Young's moduli, with stiffness correlated to the content of intermolecular hydrogen bonding and the structure transition process.
Article
Chemistry, Multidisciplinary
Jiangtao Zhou, Ting Li, Mohammad Peydayesh, Mattia Usuelli, Viviane Lutz-Bueno, Jie Teng, Li Wang, Raffaele Mezzenga
Summary: Amyloid functional materials derived from oat globulin show diverse functionalities with rich polymorphism, reversible and irreversible fibrillization processes. These materials can be applied in water purification, sensors, and electrodes, with demonstrated sustainability against other protein sources for environmentally-efficient advanced materials and technologies.
Article
Clinical Neurology
Wenting Guo, Haibo Wang, Arun Kumar Tharkeshwar, Julien Couthouis, Elke Braems, Pegah Masrori, Evelien Van Schoor, Yannan Fan, Karan Ahuja, Matthieu Moisse, Maarten Jacquemyn, Rodrigo Furtado Madeiro da Costa, Madhavsai Gajjar, Sriram Balusu, Tine Tricot, Laura Fumagalli, Nicole Hersmus, Rekin's Janky, Francis Impens, Pieter Vanden Berghe, Ritchie Ho, Dietmar Rudolf Thal, Rik Vandenberghe, Muralidhar L. Hegde, Siddharthan Chandran, Bart De Strooper, Dirk Daelemans, Philip Van Damme, Ludo Van den Bosch, Catherine Verfaillie
Summary: In this study, we identified NEK6 as a novel therapeutic target for C9orf72 FTD/ALS by performing a kinome-wide CRISPR/Cas9 knock-out screen in human induced pluripotent stem cell-derived cortical neurons. NEK6 was found to regulate poly(PR)-mediated p53-related DNA damage.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Jolien Schaeverbeke, Sandra O. Tome, Alicja Ronisz, Simona Ospitalieri, Christine A. F. von Arnim, Markus Otto, Rik Vandenberghe, Dietmar Rudolf Thal
Summary: This study quantitatively assessed neuronal density and pathology in the nucleus basalis of Meynert (nbM) of 47 cases, including different variants of primary progressive aphasia (PPA) and Alzheimer's disease (AD). The results showed that reduced nbM neuronal density was only found in AD. PPA patients with underlying AD pathology exhibited lower neuronal densities, while those with frontotemporal lobar degeneration (FTLD) were unaffected.
ALZHEIMERS & DEMENTIA
(2023)
Letter
Hematology
Devendra Hiwase, Christopher Hahn, Elizabeth Ngoc Hoa Tran, Rakchha Chhetri, Anmol Baranwal, Aref Al-Kali, Kirsty Sharplin, Dariusz Ladon, Rachel Hollins, Patricia Greipp, Monika Kutyna, Hassan Alkhateeb, Talha Badar, Paul Wang, David M. Ross, Deepak Singhal, Naranie Shanmuganathan, Peter Bardy, Ashanka Beligaswatte, David Yeung, Mark R. Litzow, Abhishek Mangaonkar, Pratyush Giri, Cindy Lee, Angie Yong, Noemi Horvath, Nimit Singhal, Raghu Gowda, William Hogan, Naseema Gangat, Mrinal Patnaik, Kebede Begna, Ing S. Tiong, Andrew Wei, Sharad Kumar, Anna Brown, Hamish Scott, Daniel Thomas, Chung H. Kok, Ayalew Tefferi, Mithun Vinod Shah
Article
Engineering, Chemical
Shuai Tan, Zechuan Zhang, Yuzhen Xue, Jingli Zhao, Junyi Ji, Caihong Wang, Yong Wu
Summary: The thermoresponsive sol-gel transitions of poly(N-isopropylacrylamide) (PNIPAm) aqueous electrolytes were investigated to provide smart overheating self-protection for energy devices. However, sol-state electrolytes are not suitable for flexible or wearable energy devices. This study successfully designed and prepared PNIPAm hydrogels cross-linked by ionic liquids, which exhibited gel-gel transitions and served as smart electrolytes and separators in flexible supercapacitors. The ionic liquid cross-linked PNIPAm hydrogel electrolytes demonstrated advanced shutdown function, providing effective overheating protection compared to conventional thermoresponsive electrolytes.
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
(2023)
Article
Biochemical Research Methods
Thomas Liepold, Hans-Wolfgang Klafki, Sathish Kumar, Jochen Walter, Oliver Wirths, Jens Wiltfang, Olaf Jahn
Summary: Amyloid-fi (Afi) peptides, including modified variants, are believed to be involved in Alzheimer's disease. However, previous studies relied on antibody-based approaches, and further analyses are needed to verify the existence of phosphorylated Afi species in brain samples using mass spectrometry. A customized matrix formulation called TOPAC was developed to improve the detection of synthetic phosphorylated Afi species. TOPAC showed higher signal intensities and minimal oxidation and loss for intact and proteolytic cleavage products, making it a valuable tool for detecting and characterizing phosphorylated Afi species in biological samples.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Article
Pediatrics
Nico Hustings, Yannick Thonissen, Lesley Cockmartin, Koen Vanderseypen, Marcella Baldewijns, Luc De Catte, Dietmar Rudolf Thal, Michael Aertsen
Summary: This study aimed to develop an MRI-based scoring system for postmortem fetal brain maceration and correlate it with autopsy results. The brain-specific maceration score showed a strong correlation with fetal brain maceration seen at histopathological exam, and different observers were able to reproduce the score reliably.
PEDIATRIC RADIOLOGY
(2023)
Article
Chemistry, Physical
Jia Chen, Jie Luo, Shuai Tan, Caihong Wang, Yong Wu
Summary: This study demonstrates that conductivities of acid hydrogels can be enhanced by regulating the polymer morphology rather than solely adjusting the acid content. The ordered polymer network with more pores and fewer barriers outperforms the random network in terms of proton conductivity. These findings shed light on the dependence of electrochemical performance on the polymer morphology of hydrogels and offer a strategy to enhance their conductivity without changing the polymer fraction.
Review
Biochemistry & Molecular Biology
Ilio Vitale, Federico Pietrocola, Emma Guilbaud, Stuart A. Aaronson, John M. Abrams, Dieter Adam, Massimiliano Agostini, Patrizia Agostinis, Emad S. Alnemri, Lucia Altucci, Ivano Amelio, David W. Andrews, Rami Aqeilan, Eli Arama, Eric H. Baehrecke, Siddharth Balachandran, Daniele Bano, Nickolai A. Barlev, Jiri Bartek, Nicolas G. Bazan, Christoph Becker, Francesca Bernassola, Mathieu J. M. Bertrand, Marco E. Bianchi, Mikhail V. Blagosklonny, J. Magarian Blander, Giovanni Blandino, Klas Blomgren, Christoph Borner, Carl D. Bortner, Pierluigi Bove, Patricia Boya, Catherine Brenner, Petr Broz, Thomas Brunner, Rune Busk Damgaard, George A. Calin, Michelangelo Campanella, Eleonora Candi, Michele Carbone, Didac Carmona-Gutierrez, Francesco Cecconi, Francis K-M Chan, Guo-Qiang Chen, Quan Chen, Youhai H. Chen, Emily H. Cheng, Jerry E. Chipuk, John A. Cidlowski, Aaron Ciechanover, Gennaro Ciliberto, Marcus Conrad, Juan R. Cubillos-Ruiz, Peter E. Czabotar, Vincenzo D'Angiolella, Mads Daugaard, Ted M. Dawson, Valina L. Dawson, Ruggero De Maria, Bart De Strooper, Klaus-Michael Debatin, Ralph J. Deberardinis, Alexei Degterev, Giannino Del Sal, Mohanish Deshmukh, Francesco Di Virgilio, Marc Diederich, Scott J. Dixon, Brian D. Dynlacht, Wafik S. El-Deiry, John W. Elrod, Kurt Engeland, Gian Maria Fimia, Claudia Galassi, Carlo Ganini, Ana J. Garcia-Saez, Abhishek D. Garg, Carmen Garrido, Evripidis Gavathiotis, Motti Gerlic, Sourav Ghosh, Douglas R. Green, Lloyd A. Greene, Hinrich Gronemeyer, Georg Haecker, Gyorgy Hajnoczky, J. Marie Hardwick, Ygal Haupt, Sudan He, David M. Heery, Michael O. Hengartner, Claudio Hetz, David A. Hildeman, Hidenori Ichijo, Satoshi Inoue, Marja Jaeaettelae, Ana Janic, Bertrand Joseph, Philipp J. Jost, Thirumala-Devi Kanneganti, Michael Karin, Hamid Kashkar, Thomas Kaufmann, Gemma L. Kelly, Oliver Kepp, Adi Kimchi, Richard N. Kitsis, Daniel J. Klionsky, Ruth Kluck, Dmitri Krysko, Dagmar Kulms, Sharad Kumar, Sergio Lavandero, Inna N. Lavrik, John J. Lemasters, Gianmaria Liccardi, Andreas Linkermann, Stuart A. Lipton, Richard A. Lockshin, Carlos Lopez-Otin, Tom Luedde, Marion MacFarlane, Frank Madeo, Walter Malorni, Gwenola Manic, Roberto Mantovani, Saverio Marchi, Jean-Christophe Marine, Seamus J. Martin, Jean-Claude Martinou, Pier G. Mastroberardino, Jan Paul Medema, Patrick Mehlen, Pascal Meier, Gerry Melino, Sonia Melino, Edward A. Miao, Ute M. Moll, Cristina Munoz-Pinedo, Daniel J. Murphy, Maria Victoria Niklison-Chirou, Flavia Novelli, Gabriel Nunez, Andrew Oberst, Dimitry Ofengeim, Joseph T. Opferman, Moshe Oren, Michele Pagano, Theocharis Panaretakis, Manolis Pasparakis, Josef M. Penninger, Francesca Pentimalli, David M. Pereira, Shazib Pervaiz, Marcus E. Peter, Paolo Pinton, Giovanni Porta, Jochen H. M. Prehn, Hamsa Puthalakath, Gabriel A. Rabinovich, Krishnaraj Rajalingam, Kodi S. Ravichandran, Markus Rehm, Jean-Ehrland Ricci, Rosario Rizzuto, Nirmal Robinson, Cecilia M. P. Rodrigues, Barak Rotblat, Carla Rothlin, David C. Rubinsztein, Thomas Rudel, Alessandro Rufini, Kevin M. Ryan, Kristopher A. Sarosiek, Akira Sawa, Emre Sayan, Kate Schroder, Luca Scorrano, Federico Sesti, Feng Shao, Yufang Shi, Giuseppe S. Sica, John Silke, Hans-Uwe Simon, Antonella Sistigu, Anastasis Stephanou, Brent R. Stockwell, Flavie Strapazzon, Andreas Strasser, Liming Sun, Erwei Sun, Qiang Sun, Gyorgy Szabadkai, Stephen W. G. Tait, Daolin Tang, Nektarios Tavernarakis, Carol M. Troy, Boris Turk, Nicoletta Urbano, Peter Vandenabeele, Tom Vanden Berghe, Matthew G. Vander Heiden, Jacqueline L. Vanderluit, Alexei Verkhratsky, Andreas Villunger, Silvia von Karstedt, Anne K. Voss, Karen H. Vousden, Domagoj Vucic, Daniela Vuri, Erwin F. Wagner, Henning Walczak, David Wallach, Ruoning Wang, Ying Wang, Achim Weber, Will Wood, Takahiro Yamazaki, Huang-Tian Yang, Zahra Zakeri, Joanna E. Zawacka-Pankau, Lin Zhang, Haibing Zhang, Boris Zhivotovsky, Wenzhao Zhou, Mauro Piacentini, Guido Kroemer, Lorenzo Galluzzi
Summary: Apoptosis is a regulated cell death process involving caspase family proteases. Inhibiting or delaying apoptosis experimentally through pharmacological and genetic strategies has demonstrated its importance in embryonic development, tissue homeostasis, and the pathogenesis of various human disorders. Defects in apoptotic cell death machinery impair development and promote oncogenesis, while inappropriate activation of apoptosis contributes to cell loss and tissue damage in neurological, cardiovascular, renal, hepatic, infectious, neoplastic, and inflammatory conditions.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Neurosciences
Sara Calafate, Gokhan Ozturan, Nicola Thrupp, Jeroen Vanderlinden, Luisa Santa-Marinha, Rafaela Morais-Ribeiro, Antonella Ruggiero, Ivan Bozic, Thomas Rusterholz, Blanca Lorente-Echeverria, Marcelo Dias, Wei-Ting Chen, Mark Fiers, Ashley Lu, Ine Vlaeminck, Eline Creemers, Katleen Craessaerts, Joris de Wit, Luuk van Boekholdt, Suresh Poovathingal, Kristofer Davie, Dietmar Rudolf Thal, Keimpe Wierda, Tiago Gil Oliveira, Inna Slutsky, Antoine Adamantidis, Bart De Strooper, Joris de Wit
Summary: Early AD is characterized by hippocampal hyperactivity and decreased sleep quality. The MCH system is involved in neuronal homeostasis but fails in the early stages of AD, leading to aberrant excitatory drive and sleep defects that compromise hippocampus-dependent functions.
NATURE NEUROSCIENCE
(2023)
Article
Oncology
Mithun Vinod Shah, Elizabeth Ngoc Hoa Tran, Syed Shah, Rakchha Chhetri, Anmol Baranwal, Dariusz Ladon, Carl Shultz, Aref Al-Kali, Anna L. Brown, Dong Chen, Hamish S. Scott, Patricia Greipp, Daniel Thomas, Hassan B. Alkhateeb, Deepak Singhal, Naseema Gangat, Sharad Kumar, Mrinal M. Patnaik, Christopher N. Hahn, Chung Hoow Kok, Ayalew Tefferi, Devendra K. Hiwase
Summary: Revised diagnostic criteria for myeloid neoplasms recommended major changes regarding TP53(mut) MN, but these changes have not been specifically examined in therapy-related myeloid neoplasm (t-MN). In this study, TP53(mut) was analyzed in 488 t-MN patients and significant findings were observed. TP53(mut) t-MN with a variant allele frequency (VAF) >= 10% had distinct clinical and biological characteristics and significantly shorter survival compared to TP53(wt) cases.
BLOOD CANCER JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Baibin Yang, Caihong Wang, Ruihan Xiang, Qiang Zhao, Yong Wu, Shuai Tan
Summary: The design of hydrogels with superior flexible deformability, anti-fracture toughness, and reliable environment adaption is important for hydrogel-based flexible devices. Soft hydrogel networks are proposed, which show good adaption to harsh saline or alkaline environments. The hydrogels have good mechanical performance and robust environment adaption, making them promising for diverse applications.
Article
Neurosciences
Nuria Suelves, Shirine Saleki, Tasha Ibrahim, Debora Palomares, Sebastiaan Moonen, Marta J. Koper, Celine Vrancx, Devkee M. Vadukul, Nicolas Papadopoulos, Nikenza Viceconte, Eloise Claude, Rik Vandenberghe, Christine A. F. von Arnim, Stefan N. Constantinescu, Dietmar Rudolf Thal, Anabelle Decottignies, Pascal Kienlen-Campard
Summary: Aging is a significant risk factor for AD, and the underlying molecular and cellular changes are not well understood. This study investigated the role of cellular senescence in AD pathology by using mouse models and human brain samples. The results showed that accelerated senescence led to early accumulation of intraneuronal Aβ and impaired autophagy function. These findings highlight the importance of senescence in AD pathophysiology and the correlation between amyloid pathology and autophagy defects.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Clinical Neurology
Grzegorz Walkiewicz, Alicja Ronisz, Rita Van Ginderdeuren, Sophie Lemmens, Femke H. Bouwman, Jeroen J. M. Hoozemans, Tjado H. J. Morrema, Annemieke J. Rozemuller, Frederique J. Hart de Ruyter, Lies De Groef, Ingeborg Stalmans, Dietmar Rudolf Thal
Summary: This study reveals the presence of a distinct primary retinal tauopathy that is different from tauopathies in the brain. The stage of retinal p-tau pathology is correlated with age, AD, and inflammation, while vision impairment is associated with underlying eye diseases and the stage of retinal p-tau pathology.
ALZHEIMERS & DEMENTIA
(2023)
Article
Pediatrics
Johannes Devos, Koenraad Devriendt, Jute Richter, Katrien Jansen, Marcella Baldewijns, Dietmar R. Thal, Michael Aertsen
Summary: This report presents the neuroimaging findings of a genetically confirmed case of fetal-onset Alexander disease, with pathological correlation after termination of pregnancy. Fetal brain magnetic resonance imaging in the third trimester is shown to be a valuable tool for diagnosing fetal-onset Alexander disease in suspected cases, in addition to neurosonography. Diffuse signal abnormalities in the periventricular white matter, thickening of the fornix and optic chiasm, as well as atypical findings such as microcephaly and cortical folding abnormalities, contribute to the phenotypic variability of Alexander disease.
PEDIATRIC RADIOLOGY
(2023)
Article
Multidisciplinary Sciences
Sriram Balusu, Katrien Horre, Nicola Thrupp, Katleen Craessaerts, An Snellinx, Lutgarde Serneels, Dries T'Syen, Iordana Chrysidou, Amaia M. Arranz, Annerieke Sierksma, Joel Simren, Thomas K. Karikari, Henrik Zetterberg, Wei-Ting Chen, Dietmar Rudolf Thal, Evgenia Salta, Mark Fiers, Bart De Strooper
Summary: Neuronal cell loss is a defining feature of Alzheimer's disease (AD), and this study reveals that the up-regulation of long noncoding RNA MEG3 is strongly associated with AD. The overexpression of MEG3 induces necroptosis in human neurons, leading to significant neuronal cell loss. However, down-regulating MEG3 or inhibiting necroptosis could rescue neuronal cell loss in a mouse model of AD, suggesting potential therapeutic approaches for AD.
