Article
Cell Biology
Sandra Roselli, Tugce Munise Satir, Rafael Camacho, Stefanie Fruhwurth, Petra Bergstrom, Henrik Zetterberg, Lotta Agholme
Summary: Alzheimer's disease (AD) is characterized by the presence of amyloid beta (Aβ)-containing plaques. The production of Aβ from amyloid precursor protein (APP) by secretases has been extensively studied, but the exact mechanism of how the interaction between APP and secretases affects APP processing is not fully understood.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2023)
Article
Neurosciences
Lauren Owens, Joshua Bracewell, Alexandre Benedetto, Neil Dawson, Christopher Gaffney, Edward Parkin
Summary: In this study, the depletion of sA beta PP alpha and the accumulation of sA beta PP alpha' were found to contribute to cytotoxicity in AD-related neuroblastoma cells overexpressing BACE1. These findings provide new insights into the pathological mechanisms of AD and raise questions about previous studies using 6E10 antibody as a biomarker.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Clinical Neurology
Yaqi Wang, Yuting Cui, Jing Liu, Qiao Song, Min Cao, Yuli Hou, Xiaomin Zhang, Peichang Wang
Summary: The upregulation of KLF5 is found to positively regulate BACE1 and accelerate APP amyloidogenic cleavage in Alzheimer's disease (AD) progression. The levels of KLF5 significantly increase in AD patients and APP/PS1 mice, and are closely related to cognitive capacity. KLF5 promotes amyloidogenic metabolism and AP synthesis through BACE1.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Article
Clinical Neurology
Eric McDade, Iryna Voytyuk, Paul Aisen, Randall J. Bateman, Maria C. Carrillo, Bart De Strooper, Christian Haass, Eric M. Reiman, Reisa Sperling, Pierre N. Tariot, Riqiang Yan, Colin L. Masters, Robert Vassar, Stefan E. Lichtenthaler
Summary: All phase III trials of BACE inhibitors for Alzheimer disease have been discontinued or produced negative results. However, the authors believe that BACE inhibitors still hold promise as a preventative therapy for AD and suggest a series of experiments to inform future trials. The authors also discuss the status of BACE inhibitors and propose ways in which the results of discontinued trials can inform the development of future clinical trials.
NATURE REVIEWS NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ruta Dekeryte, Zara Franklin, Claire Hull, Lorenzo Croce, Sarah Kamli-Salino, Oliver Helk, Philip A. Hoffmann, Zhixiang Yang, Gernot Riedel, Mirela Delibegovic, Bettina Platt
Summary: The study demonstrates the role of BACE1 in regulating systemic glucose homeostasis and suggests BACE1 inhibitors for treating T2DM-associated pathologies. LY2886721 treatment improved glucose homeostasis and hepatic insulin sensitivity in PLB4 mice, but did not show improvements in motor coordination.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Cell Biology
Barbara Bettegazzi, Laura Sebastian Monasor, Serena Bellani, Franca Codazzi, Lisa Michelle Restelli, Alessio Vittorio Colombo, Nikolaus Deigendesch, Stephan Frank, Takashi Saito, Takaomi C. Saido, Sven Lammich, Sabina Tahirovic, Fabio Grohovaz, Daniele Zacchetti
Summary: The study provides evidence for the role of Casein Kinase 2 in controlling BACE1 expression and demonstrates a mechanism linking neuronal activity with amyloid production and deposition in the brain. The findings offer new perspectives for AD treatment strategies.
CELL DEATH & DISEASE
(2021)
Article
Neurosciences
Jonathan Aow, Tzu-Rung Huang, Gopal Thinakaran, Edward H. Koo
Summary: In this study, the researchers found that there was a significant early and aberrant Bace1-mediated APP cleavage in the presence of APP/Bace1 co-expression. This led to disturbances in the trafficking of full-length APP (fl-APP) from the secretory pathway, resulting in a substantial loss of surface fl-APP and a marked reduction in APP internalization. Therefore, caution is needed when interpreting results where APP is detected only with a C-terminal tag in the presence of Bace1 co-expression, and previous findings may need to be reinterpreted if it is unclear whether fl-APP is present in normal physiological levels.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Oncology
Qing-Qing Xie, Xiao Feng, Yi-Yun Huang, Nian Fang, Hua Yi, Zi-Jian Wang, Qiao-Yu Cao, Guo-Feng Lou, Jun-Ping Pan, Yang Hu, Fang-Cheng Li, Qing Zheng, Fei Xiao
Summary: The study suggests that Nogo-A may be involved in Alzheimer's disease by promoting beta-amyloid protein secretion, potentially providing a new target for therapy. Nogo-A is known for its role as an inhibitor of neuron regeneration in the adult central nervous system, and further research is needed to understand its molecular mechanisms in Alzheimer's disease.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Xuansheng Xiao, Xiaotong Wang, Ke Zhu, Lijuan Li, Ying He, Jinglan Zhang, Linying Li, Hanning Hu, Yanqiu Cui, Jianliang Zhang, Yan Zheng
Summary: BACE1 is a key enzyme involved in the production of β-amyloid, and is considered a major drug target for Alzheimer's disease. However, BACE1 inhibitors have failed in clinical trials, and may actually worsen cognitive function, suggesting that BACE1 may play a role in regulating cognition-relevant neural circuits.
MOLECULAR PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Claudia Capitini, Alessandra Bigi, Niccolo Parenti, Marco Emanuele, Niccolo Bianchi, Roberta Cascella, Cristina Cecchi, Laura Maggi, Francesco Annunziato, Francesco Saverio Pavone, Martino Calamai
Summary: High cholesterol levels increase the shedding of amyloid precursor protein (APP) in human neuroblastoma cells, affecting its cleavage by Bace1. However, cholesterol enrichment does not affect the lateral diffusion of APP and Bace1, as demonstrated by single molecule tracking.
Article
Biochemistry & Molecular Biology
Marc R. Benoit, Mabintou Darboe, Brati Das, Yingying Ge, John Zhou, Annie Yao, Wanxia He, Riqiang Yan, Xiangyou Hu
Summary: The study reveals that neuronal BACE1 plays a critical role in the development of the central and peripheral nervous system. Deletion of BACE1 leads to impaired maturation of neural precursor cells and oligodendrocytes, as well as deficits in the trajectory of neuroblasts. Furthermore, the deficiency of BACE1 affects gene expression related to SNARE signaling, tight junction signaling, synaptogenesis, and insulin secretion pathways, resulting in deficits in synaptic functions and cognitive behaviors.
HUMAN MOLECULAR GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Matthias Koch, Thomas Enzlein, Shu-Yu Chen, Dieter Petit, Sam Lismont, Martin Zacharias, Carsten Hopf, Lucia Chavez-Gutierrez
Summary: This study explores the mechanism that controls the processing of the amyloid precursor protein (APP) by gamma-secretases, which is crucial in determining the length of amyloid-beta (A beta) peptides and their role in Alzheimer's disease (AD) pathogenesis. The researchers found that polar interactions established by the APPC99 ectodomain (ECD) play a key role in regulating the cleavage of APP by gamma-secretases. Increasing the hydrophobicity of APPC99-ECD attenuates substrate-driven product release and rescues the effects of Alzheimer's disease-associated pathogenic gamma-secretase and APP variants on A beta length. Furthermore, the study reveals that APPC99-ECD facilitates the production of longer A beta peptides caused by certain gamma-secretase inhibitors. These findings highlight the importance of the APPC99-ECD in regulating gamma-secretase activity and suggest it as a potential target for developing compounds that can selectively promote APP processing by these enzymes.
Article
Agriculture, Multidisciplinary
Jian Bao, Zheng Liang, Xiaokang Gong, Yanna Zhao, Mengjuan Wu, Wei Liu, Chenyu Tu, Xiaochuan Wang, Xiji Shu
Summary: This study found that Tangeretin (TAN) exhibits antidementia activity in APPswe/PSEN1dE9 transgenic mice, reducing cognitive impairment, synaptic impairments, and beta-amyloid accumulations. TAN also showed powerful inhibitory activity against beta-secretase, suggesting it as a potential drug for preventing Alzheimer's disease pathology.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Brati Das, Neeraj Singh, Annie Y. Yao, John Zhou, Wanxia He, Xiangyou Hu, Riqiang Yan
Summary: Our study reveals the crucial role of BACE1 in synaptic vesicle release and the impact of BACE1 inhibitors on synaptic vesicle docking in the active zones. Additionally, BACE1 deficiency results in severe reduction in hippocampal LTP and learning behaviors in mice.
MOLECULAR PSYCHIATRY
(2021)
Review
Chemistry, Medicinal
Weimin Qiu, Hui Liu, Yijun Liu, Xin Lu, Lei Wang, Yanyu Hu, Feng Feng, Qi Li, Haopeng Sun
Summary: Alzheimer's disease (AD) is a difficult to treat progressive neurodegenerative disease characterized by the accumulation of amyloid beta (A beta) plaques in the brain. A beta interacts with various receptors on the plasma membrane and mediates signaling pathways that contribute to the development of AD. Despite ongoing research, there are currently no effective medications for AD. This review discusses the importance of A beta in the pathogenesis of AD, recent progress in targeting A beta-related receptors and compounds, and the challenges and opportunities in developing effective therapies for AD.
MEDICINAL RESEARCH REVIEWS
(2023)
Article
Chemistry, Inorganic & Nuclear
Md Kamal Hossain, Joerg A. Schachner, Matti Haukka, Nadia C. Moesch-Zanetti, Ebbe Nordlander, Ari Lehtonen
INORGANICA CHIMICA ACTA
(2019)
Article
Chemistry, Inorganic & Nuclear
Md Kamal Hossain, Anja Kohntopp, Matti Haukka, Michael G. Richmond, Ari Lehtonen, Ebbe Nordlander
Correction
Chemistry, Multidisciplinary
Andrea C. Neira, Paulina R. Martinez-Alanis, Gabriel Aullon, Marcos Flores-Alamo, Paulino Zeron, Anna Company, Juan Chen, Johann B. Kasper, Wesley R. Browne, Ebbe Nordlander, Ivan Castillo
Article
Chemistry, Multidisciplinary
Md Kamal Hossain, Maxym O. Plutenko, Joerg A. Schachner, Matti Haukka, Nadia C. Moesch-Zanetti, Igor O. Fritsky, Ebbe Nordlander
Summary: The new cis-dioxomolybdenum (VI) complexes containing tridentate hydrazone-based ligands have been synthesized and evaluated for their catalytic activities in various oxidation reactions. Complexes 1 and 3 showed better catalytic performances than complex 2 due to the differences in their steric properties.
JOURNAL OF THE INDIAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Inorganic & Nuclear
Md Kamal Hossain, Joerg A. Schachner, Matti Haukka, Michael G. Richmond, Nadia C. Moesch-Zanetti, Ari Lehtonen, Ebbe Nordlander
Summary: A series of new cationic dioxidomolybdenum(VI) complexes have been synthesized and characterized, showing good reactivity in oxygen atom transfer and oxidation reactions with triphenylphosphine.
Article
Nanoscience & Nanotechnology
Chuanshuai Li, Xianshao Zou, Weihua Lin, Hassan Mourad, Jie Meng, Yang Liu, Mohamed Abdellah, Meiyuan Guo, Kaibo Zheng, Ebbe Nordlander
Summary: A g-C3N4/CdSe quantum dot/[Fe2S2(CO)(6)] composite has been successfully constructed as a highly efficient and stable photocatalyst for hydrogen evolution. The photoinduced charge carrier transfer dynamics indicate that g-C3N4 plays a crucial role in facilitating charge transfer within the composite, leading to enhanced photocatalytic activity and stability. Energy transfer from g-C3N4 to the CdSe quantum dot/[Fe2S2(CO)(6)] assembly also contributes to the overall charge transfer process.
ACS APPLIED NANO MATERIALS
(2021)
Article
Chemistry, Inorganic & Nuclear
Mainak Mitra, Alexander Brinkmeier, Yong Li, Margarida Borrell, Arnau Call, Julio Lloret Fillol, Michael G. Richmond, Miquel Costas, Ebbe Nordlander
Summary: Two new tetradentate N4 ligands and their corresponding Fe(II) complexes have been synthesized and characterized. The complexes exhibit excellent catalytic activity in the hydroxylation of alkanes and the oxidation of cyclooctene, using hydrogen peroxide as oxidant. Isotope labeling experiments provide insight into the steric influence exerted by the ligands on the relative reactivity of the oxo ligands.
DALTON TRANSACTIONS
(2023)
Article
Chemistry, Inorganic & Nuclear
Priya Singh, Yuri Lee, Jaycee R. Mayfield, Reena Singh, Melissa C. Denler, Shannon D. Jones, Victor W. Day, Ebbe Nordlander, Timothy A. Jackson
Summary: A series of manganese(II) and oxomanganese(IV) complexes with different ligand-field strengths were synthesized and characterized. The [Mn-IV(O)(N4py(Me2))]2+ complex showed the weakest equatorial ligand field, while the [Mn-IV(O)(N2py2I)]2+ complex exhibited the strongest equatorial ligand-field strength. The [Mn-IV(O)(N3pyQ)]2+ complex with quinoline and pyridine donors showed high reactivity in C-H bond and thioanisole oxidation reactions.
INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Jessica K. Elinburg, Samantha L. Carter, Joshua J. M. Nelson, Douglas G. Fraser, Michael P. Crockett, Aaron B. Beeler, Ebbe Nordlander, Arnold L. Rheingold, Linda H. Doerrer
INORGANIC CHEMISTRY
(2020)
Article
Chemistry, Multidisciplinary
Siddharth S. Matikonda, Joseph Ivanic, Miguel Gomez, Gabrielle Hammersley, Martin J. Schnermann
Article
Chemistry, Inorganic & Nuclear
Ahibur Rahaman, George C. Lisensky, Jess Browder-Long, David A. Hrovat, Michael G. Richmond, Ebbe Nordlander, Graeme Hogarth
DALTON TRANSACTIONS
(2020)
Article
Chemistry, Inorganic & Nuclear
Ahmed F. Abdel-Magied, Yusuf Theibich, Amrendra K. Singh, Ahibur Rahaman, Isa Doverbratt, Arun K. Raha, Matti Haukka, Michael G. Richmond, Ebbe Nordlander
DALTON TRANSACTIONS
(2020)
Article
Chemistry, Inorganic & Nuclear
Melissa C. Denler, Allyssa A. Massie, Reena Singh, Eleanor Stewart-Jones, Arup Sinha, Victor W. Day, Ebbe Nordlander, Timothy A. Jackson
DALTON TRANSACTIONS
(2019)
Article
Chemistry, Inorganic & Nuclear
Mainak Mitra, Olaf Cusso, Satish S. Bhat, Mingzhe Sun, Marco Cianfanelli, Miquel Costas, Ebbe Nordlander
DALTON TRANSACTIONS
(2019)
Article
Chemistry, Inorganic & Nuclear
Diana R. Melis, Christopher B. Barnett, Lubbe Wiesner, Ebbe Nordlander, Gregory S. Smith
DALTON TRANSACTIONS
(2020)