Article
Clinical Neurology
Andrew G. Murchison
Summary: This article posits that amyloid deposition and increased permeability of the blood-brain barrier are early independent events in Alzheimer's disease pathophysiology, contributing to a distinct microglial activation phenotype. Downstream effects such as synapse phagocytosis and persistent glutamate signally through NMDA receptors lead to neurodegeneration and tau pathology. This hypothesis aims to shed light on unexplained temporal and spatial features of AD by drawing from multiple lines of evidence.
ALZHEIMERS & DEMENTIA
(2022)
Article
Nanoscience & Nanotechnology
Chaoren Yan, Chaoli Wang, Xu Shao, Yonggang Teng, Peng Chen, Xiaoling Hu, Ping Guan, Hong Wu
Summary: This study proposes an innovative treatment strategy using multifunctional nanoassemblies (yCDs-Ce6) for Alzheimer's disease (AD). The yCDs-Ce6 can suppress and disaggregate amyloid aggregates, reduce cytotoxicity, and prevent microbial growth through photodynamic and photothermal therapy. Additionally, the yCDs-Ce6 can specifically target amyloid aggregates without causing significant negative effects on normal cells.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Geriatrics & Gerontology
Qing-Qing Tao, Rong-Rong Lin, Yi-He Chen, Zhi-Ying Wu
Summary: Alzheimer's disease is the most common neurodegenerative disease characterized by the accumulation of Aβ and tau in the brain. The dysfunction of the blood brain barrier (BBB) is increasingly recognized as a causative factor of cognitive impairment, but its role in the pathogenesis of AD is still not fully understood. Additional research is needed to determine the underlying mechanisms between BBB dysfunction and AD, as well as explore new therapies for BBB regulation to treat AD in the future.
Article
Clinical Neurology
Bruna Bellaver, Albert Puig-Pijoan, Joao Pedro Ferrari-Souza, Douglas T. Leffa, Firoza Z. Lussier, Pamela C. L. Ferreira, Cecile Tissot, Guilherme Povala, Joseph Therriault, Andrea L. Benedet, Nicholas J. Ashton, Stijn Servaes, Mira Chamoun, Jenna Stevenson, Nesrine Rahmouni, Marie Vermeiren, Arthur C. Macedo, Aida Fernandez-Lebrero, Greta Garcia-Escobar, Irene Navalpotro-Gomez, Oscar Lopez, Dana L. Tudorascu, Ann Cohen, Victor L. Villemagne, William E. Klunk, Serge Gauthier, Eduardo R. Zimmer, Thomas K. Karikari, Kaj Blennow, Henrik Zetterberg, Marc Suarez-Calvet, Pedro Rosa-Neto, Tharick A. Pascoal
Summary: The permeability of the blood-brain barrier (BBB) may affect the levels of brain-derived proteins in the blood, which in turn can impact the relationship between brain and blood biomarkers. The study found that BBB permeability influenced the relationship between plasma A beta(42/40) and CSF A beta(42/40) as well as A beta-PET positivity, but did not significantly impact the relationship between brain and plasma p-tau levels.
ALZHEIMERS & DEMENTIA
(2023)
Article
Cell Biology
Tong Wu, Lizhi Chen, Lingqi Zhou, Jie Xu, Kaihua Guo
Summary: Platelets may play an important role in the pathogenesis of Alzheimer's disease, as their Aβ content increases with age and aged platelets can accelerate Aβ deposition in the brain, leading to learning and memory deficits in recipient mice. Administering aspirin as a platelet activation inhibitor effectively alleviated these toxic processes. In vitro blood-brain barrier models were used to explore the possible cytotoxicity of these platelets.
Article
Biochemistry & Molecular Biology
Sofia Toniolo, Francesco Di Lorenzo, Sergio Bernardini, Nicola Biagio Mercuri, Giulia Maria Sancesario
Summary: The definition of Alzheimer's disease (AD) now includes the presence of amyloid (A), tau deposition (T), and neurodegeneration (N) markers as essential for diagnosis. The relationship between blood-brain barrier (BBB) dysfunction and AD-specific biomarkers needs attention as blood-based biomarkers are being used more frequently. Factors such as age, gender, and ApoE status have previously been linked to BBB permeability. In this study, BBB dysfunction was not different across ATN subtypes and was not correlated with cognitive impairment, but patients with BBB disruption had low levels of A beta 40, and ApoE status affected the A beta 42/40 ratio.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Ruiyi Zhou, Lihong Zhu, Zhaohao Zeng, Rixin Luo, Jiawei Zhang, Rui Guo, Lei Zhang, Qunying Zhang, Wei Bi
Summary: In this study, a brain-targeted nanomedicine was designed for the treatment of Alzheimer's disease. The results showed that the nanomedicine had favorable biocompatibility and could effectively reduce amyloid deposition, improve neuronal damage, and enhance learning and memory capability.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Bibiana C. Mota, Nathan Ashburner, Laura Abelleira-Hervas, Liyueyue Liu, Robertas Aleksynas, Lucio Claudio Rovati, Gianfranco Caselli, Magdalena Sastre
Summary: Recent evidence suggests that I2-imidazoline ligands have neuroprotective properties in animal models of neurodegeneration, such as Alzheimer's disease (AD). In this study, the therapeutic potential of the powerful analgesic I2-imidazoline ligand CR4056 in the 5xFAD model of AD was evaluated. The results showed that CR4056 improved recognition memory, suppressed pro-inflammatory microglia, and restored fibrinogen extravasation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Kassandra Kisler, Abhay P. Sagare, Divna Lazic, Sam Bazzi, Erica Lawson, Ching-Ju Hsu, Yaoming Wang, Anita Ramanathan, Amy R. Nelson, Zhen Zhao, Berislav V. Zlokovic
Summary: PICALM is a significant susceptibility factor for Alzheimer's disease and plays a role in Aβ clearance at the blood-brain barrier. The anti-malaria drug artesunate can increase PICALM levels, reduce Aβ deposition, and improve cerebral blood flow and behavior in mice. This research is important for the treatment of Alzheimer's disease.
MOLECULAR NEURODEGENERATION
(2023)
Article
Chemistry, Multidisciplinary
Yipeng Zhao, Siyu Tian, Jie Zhang, Xi Cheng, Wenping Huang, Guoliang Cao, Yan-Zhong Chang, Hai Wang, Guangjun Nie, Wei Qiu
Summary: Using modified liraglutide nanostructures can inhibit neuroinflammation and promote the differentiation of astrocytes into protective cell types, thereby significantly alleviating the progression of Alzheimer's disease.
Article
Materials Science, Multidisciplinary
Shiting Song, Jingwen Wu, Ying Cheng, Lixiang Ma, Tao Liu, Jia Liu, Jun Liu, Jaroslaw Sotor, Ping Luan
Summary: Two-dimensional nanomaterials have shown potential in pharmaceutical applications, especially in the diagnosis and treatment of Alzheimer's disease (AD). They can improve the accuracy and specificity of AD biomarkers detection and inhibit A beta aggregation in treatment. However, resolving in vivo cytotoxicity remains a challenge.
APPLIED MATERIALS TODAY
(2021)
Article
Clinical Neurology
Haoshen Shi, Yosef Koronyo, Dieu-Trang Fuchs, Julia Sheyn, Ousman Jallow, Krishna Mandalia, Stuart L. Graham, Vivek K. Gupta, Mehdi Mirzaei, Andrei A. Kramerov, Alexander V. Ljubimov, Debra Hawes, Carol A. Miller, Keith L. Black, Roxana O. Carare, Maya Koronyo-Hamaoui
Summary: This study found that vascular amyloid beta (Aβ) protein deposits were detected in retinas of mild cognitively impaired (MCI) and Alzheimer's disease (AD) patients, and these deposits were linked to disease status. The study also revealed that the components of retinal vascular tight junctions (TJs) and Aβ expression were correlated with neuropathology. The severe decreases in retinal vascular zonula occludens-1 (ZO-1) and claudin-5 were identified in MCI and AD patients, which correlated with arteriolar Aβ(40) deposition and cerebral pathology and cognitive deficits.
ALZHEIMERS & DEMENTIA
(2023)
Article
Medicine, Research & Experimental
Zengtao Wang, Nidhi Sharda, Geoffry L. Curran, Ling Li, Val J. Lowe, Karunya K. Kandimalla
Summary: This study utilized dynamic imaging and pharmacokinetic modeling to investigate the accumulation kinetics of A beta peptides in the blood-brain barrier (BBB) endothelium. The results show that A beta 42 accumulates at a lower rate than A beta 40, and model simulations suggest that impaired exocytosis of A beta 42 leads to increased accumulation within the BBB endothelium.
MOLECULAR PHARMACEUTICS
(2021)
Article
Nanoscience & Nanotechnology
Xian Guo, Qiaoshan Lie, Yanan Liu, Zhi Jia, Youcong Gong, Xiaoyu Yuan, Jie Liu
Summary: SeQDs, as a novel drug with multi-target therapeutic effects, show significant advantages in the treatment of Alzheimer's disease, including rapid penetration of the blood-brain barrier, inhibition of Aβ aggregation, reduction of tau protein phosphorylation, and reduction of oxidative stress, ultimately improving cognitive and memory abilities in AD patients.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Chemistry, Multidisciplinary
Tao Sun, Qiaoqiao Shi, Yongzhi Zhang, Chanikarn Power, Camilla Hoesch, Shawna Antonelli, Maren K. Schroeder, Barbara J. Caldarone, Nadine Taudte, Mathias Schenk, Thore Hettmann, Stephan Schilling, Nathan J. McDannold, Cynthia A. Lemere
Summary: The use of focused ultrasound (FUS) with microbubbles enhanced the delivery of an Fc-competent anti-pGlu3 Aβ monoclonal antibody to the brain, resulting in improved cognitive function and reduced plaque burden in aged Alzheimer's disease-like model mice. Additionally, the combination of antibody treatment with FUS-BBBD led to greater monocyte infiltration to plaques, suggesting a potential novel mechanism for enhancing immunotherapy efficacy in Alzheimer's disease.
JOURNAL OF CONTROLLED RELEASE
(2021)
Review
Clinical Neurology
Yvonne Reiss, Sebastian Bauer, Bastian David, Kavi Devraj, Elif Fidan, Elke Hattingen, Stefan Liebner, Nico Melzer, Sven G. Meuth, Felix Rosenow, Theodor Rueber, Laurent M. Willems, Karl H. Plate
Summary: The blood-brain barrier (BBB) is a crucial physiological barrier that maintains the brain microenvironment necessary for proper neuronal function. Dysfunction of the BBB is a characteristic of neurological diseases including ischemia, brain tumors, neurodegenerative diseases, infections, and autoimmune neuroinflammatory disorders. Additionally, BBB dysfunction is involved in epilepsy, a brain disorder characterized by synchronized neuronal activity and seizures. While antiseizure drugs targeting neuronal hyperexcitability are not always effective, drugs specifically targeting the neurovasculature in epilepsy patients have not been explored. Understanding the mechanism of BBB compromise in epilepsy is important for its therapeutic potential.
Article
Chemistry, Multidisciplinary
Julian Kompa, Jorick Bruins, Marius Glogger, Jonas Wilhelm, Michelle S. Frei, Miroslaw Tarnawski, Elisa D'Este, Mike Heilemann, Julien Hiblot, Kai Johnsson
Summary: The specific and covalent labeling of the protein HaloTag with fluorescent probes in living cells makes it a powerful tool for bioimaging. However, the irreversible attachment of the probe to HaloTag precludes imaging applications that require transient binding of the probe and comes with the risk of irreversible photobleaching. Here, we introduce exchangeable ligands for fluorescence labeling of HaloTag (xHTLs) that reversibly bind to HaloTag and that can be coupled to rhodamines of different colors.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Correction
Clinical Neurology
Lucas Hoffmann, Roland Coras, Katja Kobow, Javier A. A. Lopez-Rivera, Dennis Lal, Costin Leu, Imad Najm, Peter Nuernberg, Jochen Herms, Patrick N. N. Harter, Christian G. G. Bien, Thilo Kalbhenn, Markus Mueller, Tom Pieper, Till Hartlieb, Manfred Kudernatsch, Hajo Hamer, Sebastian Brandner, Karl Roessler, Ingmar Bluemcke, Samir Jabari
ACTA NEUROPATHOLOGICA
(2023)
Article
Clinical Neurology
Lucas Hoffmann, Roland Coras, Katja Kobow, Javier A. Lopez-Rivera, Dennis Lal, Costin Leu, Imad Najm, Peter Nuernberg, Jochen Herms, Patrick N. Harter, Christian G. Bien, Thilo Kalbhenn, Markus Mueller, Tom Pieper, Till Hartlieb, Manfred Kudernatsch, Hajo Hamer, Sebastian Brandner, Karl Roessler, Ingmar Bluemcke, Samir Jabari
Summary: Exome-wide sequencing studies have identified PTPN11 as a novel brain somatic epilepsy gene, while germline mutations of PTPN11 cause Noonan syndrome. In this study, the authors analyzed ganglioglioma (GG) with PTPN11 alterations and compared them to GG with BRAFV600E mutations. They found that GG with PTPN11 alterations had adverse postsurgical outcome and distinct genetic characteristics.
ACTA NEUROPATHOLOGICA
(2023)
Review
Chemistry, Multidisciplinary
Lorenzo Albertazzi, Mike Heilemann
Summary: The exploitation of low-affinity molecular interactions in protein labeling is an emerging topic in optical microscopy, which allows for a constant renewal of fluorescence signals at target sites. It has versatile use across microscopy methods and has shown potential in 3D, live, and many-target applications. Although some progress has been made in developing low-affinity labels, this research field still has a lot of untapped potential.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Claudia Catapano, Johanna V. Rahm, Marjan Omer, Laura Teodori, Jorgen Kjems, Marina S. Dietz, Mike Heilemann
Summary: HER2 belongs to the ErbB sub-family of receptor tyrosine kinases and is activated through heterodimerization with other ErbB receptors. This study found that HER2 is strongly activated by EGFR-targeting ligands EGF and TGFa, with a distinguishable temporal fingerprint. HER4-targeting ligands EREG and NRG beta 1 showed weaker activation of HER2, with a preference for EREG and a delayed response to NRG beta 1.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biodiversity Conservation
Anna C. Schleimer, Alain Frantz, Lorraine Richart, Joerg Mehnert, Gono Semiadi, Michel Wirdateti, Johanna Rode-Margono, Michel Mittelbronn, Stuart Young, Frank Drygala
Summary: This study demonstrates how biogeographic processes and human activities can significantly impact species conservation. The Bawean pig was found to have diverged at least 166 k years ago and is currently facing a small population size. Additionally, the Javan pig showed evidence of secondary contact with another pig species. Immediate action should be taken to protect both species.
DIVERSITY AND DISTRIBUTIONS
(2023)
Article
Multidisciplinary Sciences
Martina Sola, Azucena Rendon-Angel, Viviana Rojo Martinez, Jacopo Sgrignani, Claudia Magrin, Ester Piovesana, Andrea Cavalli, Paolo Paganetti, Stephanie Papin
Summary: Mutations in the Tau gene cause progressive dementia and the deposition of neurotoxic Tau forms in neurofibrillary tangles is a characteristic feature of neurodegenerative tauopathies. Loss of non-canonical Tau functions may contribute to disease. Additionally, Tau interacts with MDM2 and affects P53 activity, and aberrant accumulation of MDM2 in neurofibrillary tangles suggests a potential role in neurodegeneration. These findings highlight a novel loss-of-function of Tau in both neurodegeneration and cancer.
SCIENTIFIC REPORTS
(2023)
Article
Dentistry, Oral Surgery & Medicine
Bob Biewer, Eric Rompen, Michel Mittelbronn, Gael P. Hammer, Pascale Quatresooz, Felix Kleine Borgmann
Summary: This in vivo study examined the effect of minocycline-HCl administration and calvaria perforation on extra-skeletal bone generation. The results showed a continuous increase in tissue fill over time in all groups. The combination of minocycline-HCl administration and calvaria perforation resulted in the strongest tissue augmentation and the most mineralized tissue, indicating an enhancing effect on vertical bone augmentation.
Article
Chemistry, Multidisciplinary
Laurell F. F. Kessler, Ashwin Balakrishnan, Nina S. S. Deussner-Helfmann, Yunqing Li, Maximilian Mantel, Marius Glogger, Hans-Dieter Barth, Marina S. S. Dietz, Mike Heilemann
Summary: Super-resolution techniques such as SMLM and STED microscopy are enhanced by using weak affinity-based transient labelling systems, such as DNA-based hybrid systems. However, these techniques suffer from high background fluorescence signal caused by unbound fluorophore-labelled oligonucleotides. This study introduces short-distance self-quenching in fluorophore dimers as an efficient mechanism to reduce background fluorescence signal and increase photon budget in the bound state.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Manuela Perez-Berlanga, Vera Wiersma, Aurelie Zbinden, Laura De Vos, Ulrich Wagner, Chiara Foglieni, Izaskun Mallona, Katharina M. Betz, Antoine Clery, Julien Weber, Zhongning Guo, Ruben Rigort, Pierre de Rossi, Ruchi Manglunia, Elena Tantardini, Sonu Sahadevan, Oliver Stach, Marian Hruska-Plochan, Frederic H-T Allain, Paolo Paganetti, Magdalini Polymenidou
Summary: Aggregation of the RNA-binding protein TDP-43 is the key neuropathological feature of neurodegenerative diseases. Our study reveals that oligomerization and RNA binding play important roles in TDP-43 stability, function, and subcellular localization. We also found that the location of TDP-43 aggregates is determined by different pathways, shedding light on the origins of pathological species observed in TDP-43 proteinopathy patients.
Article
Biochemistry & Molecular Biology
Leonora Szabo, Nadia Cummins, Paolo Paganetti, Alex Odermatt, Andreas Papassotiropoulos, Celeste Karch, Jurgen Gotz, Anne Eckert, Amandine Grimm
Summary: Abnormal tau protein disrupts the interaction between the endoplasmic reticulum (ER) and mitochondria, leading to impaired mitochondrial function and cholesterol metabolism. This study shows that abnormal tau loosens the association between ER and mitochondria, particularly through the VAPB-PTPIP51 pathway. Disruption of the ER-mitochondria interaction results in altered levels of mitochondrial cholesterol and pregnenolone, which can be restored by inhibiting GSK3 beta.
Article
Biochemical Research Methods
Alon Saguy, Onit Alalouf, Nadav Opatovski, Soohyen Jang, Mike Heilemann, Yoav Shechtman
Summary: Single-molecule localization microscopy (SMLM) has significantly improved spatial resolution in biological imaging, but has limitations in observing dynamics at high temporal resolution. In this study, we introduce DBlink, a deep-learning-based method that reconstructs super spatiotemporal resolution videos from SMLM data. DBlink utilizes a convolutional neural network combined with a bidirectional long short-term memory network to capture long-term dependencies between different frames. Experimental results demonstrate the effectiveness of DBlink in various scenarios, including simulated structures and live-cell dynamic SMLM. This advancement in super-resolution imaging of dynamic processes in living cells is crucial.
Article
Oncology
Ernesto Gargiulo, Elodie Viry, Pablo Elias Morande, Anne Largeot, Susanne Gonder, Feng Xian, Nikolaos Ioannou, Mohaned Benzarti, Felix Bruno Kleine Borgmann, Michel Mittelbronn, Gunnar Dittmar, Petr Nazarov, Johannes Meiser, Basile Stamatopoulos, Alan G. Ramsay, Etienne Moussay, Jerome Paggetti
Summary: This study investigated the interactions between cancer cells and the microenvironment using mouse models of chronic lymphocytic leukemia (CLL). It found that small extracellular vesicles (sEVs) derived from CLL tissue contain specific miRNA and immune-checkpoint ligands, which alter the function and exhaustion of CD8+ T cells. Blocking sEV biogenesis delayed CLL pathogenesis and high expression of sEV-related genes correlated with poor outcomes in CLL patients.
BLOOD CANCER DISCOVERY
(2023)
Article
Biophysics
Soohyen Jang, Kaarjel K. Narayanasamy, Johanna V. Rahm, Alon Saguy, Julian Kompa, Marina S. Dietz, Kai Johnsson, Yoav Shechtman, Mike Heilemann
Summary: Single-molecule localization microscopy achieves nanometer spatial resolution but faces challenges of long acquisition time and photobleaching. This study combines a neural network and a protein labeling method to improve acquisition speed and temporal resolution, enabling capturing of cellular structure dynamics in live cells.
BIOPHYSICAL REPORTS
(2023)