Article
Multidisciplinary Sciences
Naoto Watamura, Kaori Sato, Gen Shiihashi, Ayami Iwasaki, Naoko Kamano, Mika Takahashi, Misaki Sekiguchi, Naomi Mihira, Ryo Fujioka, Kenichi Nagata, Shoko Hashimoto, Takashi Saito, Toshio Ohshima, Takaomi C. Saido, Hiroki Sasaguri
Summary: Devoid of the Swedish mutations, the newly generated App knock-in mice (App(G-F) mice) show characteristics suitable for preclinical studies of beta-secretase inhibition in Alzheimer's disease (AD). Comparison of isogenic App knock-in lines reveals the influence of factors like C-terminal fragment beta (CTF-beta) and humanization of A beta on endosomal alterations.
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
Medicine, General & Internal
Emmanuelle Albalat, Thibault Cavey, Patricia Leroyer, Martine Ropert, Vincent Balter, Olivier Loreal
Summary: Hereditary hemochromatosis is a genetic iron overload disease caused by a mutation in the HFE gene. Using Hfe(-/-) mice, this study found that the concentration of iron and stable isotope composition increased in the liver and red blood cells, but not in the spleen. The results suggest that the increase in whole blood isotope composition in hemochromatosis patients is mainly due to the release of heavy isotope-enriched iron from the liver, rather than increased dietary iron absorption.
FRONTIERS IN MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Luana Naia, Makoto Shimozawa, Erika Bereczki, Xidan Li, Jianping Liu, Richeng Jiang, Romain Giraud, Nuno Santos Leal, Catarina Moreira Pinho, Erik Berger, Victoria Lim Falk, Giacomo Dentoni, Maria Ankarcrona, Per Nilsson
Summary: This study investigates the sequential onset of AD-like pathologies in App knock-in mice and reveals that energy metabolism is significantly altered at an early stage of pathology. As the pathology progresses, the brain shifts to a state of hypometabolism and synaptic abnormalities occur, including accumulation of synaptic vesicles and autophagosomes.
MOLECULAR PSYCHIATRY
(2023)
Article
Pharmacology & Pharmacy
Yousif Aldabbagh, Anam Islam, Weicong Zhang, Paul Whiting, Afia B. Ali
Summary: In this study, the researchers investigated the alteration of astrocyte-specific GABA transporter 3/4 (GAT3/4) in a mouse model of Alzheimer's disease (AD) and its correlation with changes in excitability of principal cells. They found increased expression of GAT3/4 in reactive astrocytes in the hippocampus of AD mice, which was correlated with enhanced tonic inhibition. Blocking GAT3/4 resulted in increased excitability of principal cells in both wild-type and AD mice, exacerbating synaptic hyperactivity. This suggests that reducing tonic inhibition through GAT3/4 may not be an effective therapeutic strategy for AD.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Neurosciences
Ceren Emre, Khanh Do, Bokkyoo Jun, Erik Hjorth, Silvia Gomez Alcalde, Marie-Audrey Kautzmann, William C. Gordon, Per Nilsson, Nicolas G. Bazan, Marianne Schultzberg
Summary: This study investigated lipid and cytokine profiles, glial activation, and inflammatory proteins in an APP knock-in AD mouse model. It found age-specific changes in the brain lipidome, with increased pro-inflammatory and pro-resolving lipid mediators only in older age groups despite early Aβ pathology. Additionally, alterations in phospholipids signaled early pathological changes in membrane composition.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Neurosciences
Dan Xia, Steve Lianoglou, Thomas Sandmann, Meredith Calvert, Jung H. Suh, Elliot Thomsen, Jason Dugas, Michelle E. Pizzo, Sarah L. DeVos, Timothy K. Earr, Chia-Ching Lin, Sonnet Davis, Connie Ha, Amy Wing-Sze Leung, Hoang Nguyen, Roni Chau, Ernie Yulyaningsih, Isabel Lopez, Hilda Solanoy, Shababa T. Masoud, Chun-chi Liang, Karin Lin, Giuseppe Astarita, Nathalie Khoury, Joy Yu Zuchero, Robert G. Thorne, Kevin Shen, Stephanie Miller, Jorge J. Palop, Dylan Garceau, Michael Sasner, Jennifer D. Whitesell, Julie A. Harris, Selina Hummel, Johannes Gnorich, Karin Wind, Lea Kunze, Artem Zatcepin, Matthias Brendel, Michael Willem, Christian Haass, Daniel Barnett, Till S. Zimmer, Anna G. Orr, Kimberly Scearce-Levie, Joseph W. Lewcock, Gilbert Di Paolo, Pascal E. Sanchez
Summary: This study created a novel App knock-in mouse model and found that microglia with fibrillar A beta were associated with lipid dyshomeostasis, lysosomal dysfunction, foam cell phenotypes, and immuno-metabolic perturbations, offering new avenues for investigating metabolic pathways in microglia responding to AD-relevant pathogenesis. The in-depth characterization of pathological hallmarks of AD in this model provides a valuable resource for further research on disease-relevant biology.
MOLECULAR NEURODEGENERATION
(2022)
Article
Cell Biology
Sudhir Kshirsagar, Rainier Vladlen Alvir, Ashly Hindle, Subodh Kumar, Murali Vijayan, Jangampalli Adi Pradeepkiran, Arubala P. Reddy, Bhagavathi Ramasubramanian, P. Hemachandra Reddy
Summary: The purpose of this study is to investigate the early cellular, molecular, morphological, and behavioral changes in humanized amyloid-beta-knock-in (hAbKI) mice. The findings suggest that amyloid-beta is sufficient to cause behavioral, mitochondrial, synaptic, and ultrastructural changes in mice.
Article
Chemistry, Applied
Nemanja Mijin, Jelica Milosevic, Sanja Stevanovic, Predrag Petrovic, Aleksandar Lolic, Tomaz Urbic, Natalija Polovic
Summary: The aggregation of proteins into fibrillar, amyloid-like aggregates has positive effects on various technological properties of food products. Heavy metal ions, such as lead and cadmium, can influence this aggregation process and alter the morphology of the aggregates. This study investigated the impact of lead and cadmium ions on the aggregation of ovalbumin, a model protein, under high temperature and acidic conditions. The results demonstrated that the binding of these metal ions to ovalbumin affected the structure and morphology of the resulting amyloid-like aggregates.
FOOD HYDROCOLLOIDS
(2023)
Article
Cell Biology
Yumeng La, Wenghong Wong, Kexin Peng, Zhen Tian, Jiewen Pan, Ruilin Sun, Jing Luan, Kexiang Yan, Qiaoan Zhang, Zhenghua Zhang
Summary: The MVD c.746 T > C mutation was found to be the most common genetic variation among Chinese PK patients. A Mvd(F250S/+) mouse model was developed using CRISPR/Cas9 technology, and showed reduced susceptibility to skin acute inflammation and activated autophagy upon IMQ induction.
Article
Biochemistry & Molecular Biology
Phan H. Truong, Peter J. Crouch, James B. W. Hilton, Catriona A. McLean, Roberto Cappai, Giuseppe D. Ciccotosto
Summary: The study demonstrates a significant role of APLP2 in MND, with APLP2 deletion delaying disease progression and increasing survival rate. Female SOD1-G37R:APLP2-/- mice showed improved neuromuscular junction innervation and muscle fiber condition.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
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
David Baglietto-Vargas, Stefania Forner, Lena Cai, Alessandra C. Martini, Laura Trujillo-Estrada, Vivek Swarup, Marie Minh Thu Nguyen, Kelly Do Huynh, Dominic Javonillo, Kristine Minh Tran, Jimmy Phan, Shan Jiang, Eniko A. Kramar, Cristina Nunez-Diaz, Gabriela Balderrama-Gutierrez, Franklin Garcia, Jessica Childs, Carlos J. Rodriguez-Ortiz, Juan Antonio Garcia-Leon, Masashi Kitazawa, Mohammad Shahnawaz, Dina P. Matheos, Xinyi Ma, Celia Da Cunha, Ken C. Walls, Rahasson R. Ager, Claudio Soto, Antonia Gutierrez, Ines Moreno-Gonzalez, Ali Mortazavi, Andrea J. Tenner, Grant R. MacGregor, Marcelo Wood, Kim N. Green, Frank M. LaFerla
Summary: The researchers created a mouse model that expresses wildtype human A β, demonstrating effects on cognition, synaptic plasticity, brain changes, inflammation, PAS granules, and gene expression. Furthermore, excision of exon 14 through Cre-mediated methods reduced A β expression and rescued cognitive impairments.
NATURE COMMUNICATIONS
(2021)
Article
Clinical Neurology
Emelie Andersson, Nina Schultz, Takashi Saito, Takaomi C. Saido, Kaj Blennow, Gunnar K. Gouras, Henrik Zetterberg, Oskar Hansson
Summary: This study investigated the relationship between A beta 42/A beta 40 ratios and cerebral A beta pathology using App knock-in mouse models. The results showed a negative association between A beta 42/A beta 40 ratios and cerebral A beta plaque burden in App(NL-F/NL-F) mice, with stronger correlations observed in CSF compared to serum. Additionally, the decline in A beta 42/A beta 40 ratios in CSF and serum occurred after the deposition of A beta aggregates in the brain reached significance. However, no similar changes were observed in App(NL/NL) mice.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Clinical Neurology
Hee Yang Lee, Soljee Yoon, Jeong Hwa Lee, Keunwan Park, Youngeun Jung, Illhwan Cho, Donghee Lee, Jisu Shin, Kyeonghwan Kim, Sunmi Kim, Jimin Kim, Koeun Kim, Seung Hoon Han, Seong Muk Kim, Hye Ju Kim, Hye Yun Kim, Ikyon Kim, Young Soo Kim
Summary: The study identified YIAD002 as a potent dissociator of Aβ aggregates, showing significant reduction in amyloid burden, improved cognitive performance, and alleviated major pathological hallmarks of AD. Mechanism studies suggest that YIAD002 interferes with intermolecular beta-sheet fibrillation by directly interacting with specific domains of Aβ.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Article
Multidisciplinary Sciences
Ariel M. Alperstein, Joshua S. Ostrander, Tianqi O. Zhang, Martin T. Zanni
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Editorial Material
Chemistry, Multidisciplinary
Kieran M. Farrell, Martin T. Zanni
ACS CENTRAL SCIENCE
(2019)
Article
Chemistry, Physical
Megan K. Petti, Joshua S. Ostrander, Erin R. Birdsall, Miriam Bohlmann Kunz, Zachary T. Armstrong, Ariel M. Alperstein, Martin T. Zanni
JOURNAL OF PHYSICAL CHEMISTRY A
(2020)
Article
Chemistry, Physical
Caitlyn R. Fields, Sidney S. Dicke, Megan K. Petti, Martin T. Zanni, Justin P. Lomont
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2020)
Article
Optics
Kieran M. Farrell, Josh S. Ostrander, Andrew C. Jones, Baichhabi R. Yakami, Sidney S. Dicke, Chris T. Middleton, Peter Hamm, Martin T. Zanni
Article
Chemistry, Physical
Sidney S. Dicke, Ariel M. Alperstein, Kathryn L. Schueler, Donald S. Stapleton, Shane P. Simonett, Caitlyn R. Fields, Farzaneh Chalyavi, Mark P. Keller, Alan D. Attie, Martin T. Zanni
Summary: This study used two-dimensional IR bioimaging to analyze the structural heterogeneity of formalin-fixed mouse pancreas. The results showed an increase in beta-sheet content in the samples over time, indicating protein aggregation. The study suggests that formalin fixation does not completely stop the degradation of protein structure in pancreas tissue.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Multidisciplinary Sciences
Kieran M. Farrell, Nan Yang, Martin T. Zanni
Summary: Two-dimensional (2D) optical spectroscopy contains cross-peaks that are helpful features for determining molecular structure and monitoring energy transfer. A polarization scheme can remove the diagonal peaks in 2D spectroscopy and the intense bleach/stimulated emission peaks in transient absorption (TA) spectroscopy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Physical
Kieran M. M. Farrell, Martin T. T. Zanni
Summary: We demonstrate the first phase stable measurement of a third-order 2Q spectrum using a pulse shaper in the pump-probe geometry. By permuting the time-ordering of the pump pulses, the signal pathways emitted in the probe direction are rearranged, achieving this measurement. We also measure a fifth-order absorptive 2Q spectrum in the pump-probe geometry, improving signal quality by minimizing saturation-induced artifacts of the pulse shaper.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Chemistry, Physical
Ryan E. Leighton, Ariel M. Alperstein, David Punihaole, W. Ruchira Silva, Renee R. Frontiera
Summary: Super-resolution fluorescence microscopy plays a crucial role in understanding the nanoscale structure of biological systems, but the use of fluorescent labels brings challenges. Therefore, label-free super-resolution techniques like stimulated Raman scattering (SRS) and stimulated Raman depletion microscopy (SRDM) have attracted great interest. This study demonstrates suppression mechanisms in SRDM and explores super-resolution Raman microscopy on different sides of the spectrum. The findings lead to the development of inverse raman depletion microscopy (IRDM) and offer label-free super-resolution imaging over a wide spectral range.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Biochemistry & Molecular Biology
Sidney S. Dicke, Michal Maj, Caitlyn R. Fields, Martin T. Zanni
Summary: The aggregation of human islet amyloid polypeptide (hIAPP) into amyloid fibrils, involving the formation of oligomeric intermediates, may be responsible for the cytotoxicity in type 2 diabetes. This study investigates the structural kinetics of aggregation in the presence of membranes using 2D IR spectroscopy and isotope labeling. The results show that the oligomeric intermediates formed in the presence of phospholipid vesicles have a similar structure to those in solution, which are considered to be the toxic species.
RSC CHEMICAL BIOLOGY
(2022)