Article
Biology
Lukas P. Feilen, Shu-Yu Chen, Akio Fukumori, Regina Feederle, Martin Zacharias, Harald Steiner
Summary: The activity of intramembrane proteases is modulated by lipid bilayers, and this study reveals the mechanism linking lipid environment to structural dynamics. The lipid bilayer plays a critical role in stabilizing the structure and arranging the active site of intramembrane protease.
Article
Neurosciences
Hirotaka Watanabe, Kent Imaizumi, Tetsuo Cai, Zhi Zhou, Taisuke Tomita, Hideyuki Okano
Summary: Genetic mutations in presenilin genes (PS1, PS2) are associated with familial Alzheimer's disease (AD). This study investigated the physiological roles of PS in human neurons using iPSCs and generated PS-null human cortical neurons. PS was found to play essential roles in Notch signaling and Aβ production, with PS1 and PS2 showing different effects on cleavage of different substrates.
Article
Cell Biology
Tobias A. Weber, Johan Lundkvist, Johanna Wanngren, Hlin Kvartsberg, ShaoBo Jin, Pia Larssen, Dan Wu, Daniel Oliveira, Karolina Minta, Gunnar Brinkmalm, Henrik Zetterberg, Kaj Blennow, Gunnar Nordvall, Bengt Winblad, Erik Portelius, Helena Karlstrom
Summary: The study demonstrates that gamma-secretase modulators selectively affect the production of Aβ, with a particular modulation on the Aβ-like proteins derived from EphA4.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Dieter Petit, Manuel Hitzenberger, Matthias Koch, Sam Lismont, Katarzyna Marta Zoltowska, Thomas Enzlein, Carsten Hopf, Martin Zacharias, Lucia Chavez-Gutierrez
Summary: This study investigates the interactions between an imidazole-based GSM and its target gamma-secretase-APP, and reveals that a part of the modulator interacts with a binding site on gamma-secretase, triggering rearrangements and stabilizing enzyme-substrate interactions.
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
Neurosciences
Ye-Ran Wang, Meng-Ting Wang, Xiao-Qin Zeng, Yu-Hui Liu, Yan-Jiang Wang
Summary: This study found lower plasma levels of NAbs-PS1 in AD patients, which were negatively associated with brain A beta load and positively associated with cognitive functions. Plasma NAbs-PS1 could be potential biomarkers for distinguishing AD patients from non-AD cognitive impairment subjects.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Neurosciences
Masato Maesako, Mei C. Q. Houser, Yuliia Turchyna, Michael S. Wolfe, Oksana Berezovska
Summary: In this study, we used a novel imaging method to visualize the subcellular compartment where γ-secretase primarily cleaves C99 to generate Aβ in mouse cortical neurons. Our findings suggest that γ-secretase processes C99 mainly in low-pH compartments and Aβ is accumulated in the same subcellular loci. Additionally, we found a functional correlation between endo-lysosomal pH and cellular γ-secretase activity.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Pharmacology & Pharmacy
Salma Nasser, Dalaal M. Abdallah, Kawkab A. Ahmed, Yousra Abdel-Mottaleb, Hanan S. El-Abhar
Summary: The study investigated the impact of mirabegron and/or carvedilol on ulcerative colitis, finding that these drugs can improve inflammation cascade, fibrotic processes, and gut barrier function by modulating various signaling pathways and molecular mechanisms to exert anti-colitic effects.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Courtney Alexander, Thomas Li, Yorito Hattori, Danica Chiu, Georgia R. Frost, Lauren Jonas, Chenge Liu, Corey J. Anderson, Eitan Wong, Laibaik Park, Costantino Iadecola, Yue-Ming Li
Summary: Hif-1α transcriptionally upregulates BACE1 and nontranscriptionally activates γ-secretase to promote amyloid-beta production in hypoxic-ischemic conditions, leading to increased risk for Alzheimer's disease (AD).
MOLECULAR PSYCHIATRY
(2022)
Review
Pharmacology & Pharmacy
Suvadeep Mal, Udita Malik, Dilipkumar Pal, Abhishek Mishra
Summary: Neurodegenerative disorders result in the progressive degeneration and death of nerve cells, with Alzheimer's disease being the most common irreversible brain disorder associated with the aggregated form of amyloid beta. The gamma-secretase complex and its inhibitors are discussed as potential solutions for preventing AD.
CURRENT DRUG TARGETS
(2021)
Article
Geriatrics & Gerontology
Marcella Catania, Alessandro Marti, Giacomina Rossi, Anna Fioretti, Chiara Boiocchi, Martina Ricci, Federico Gasparini, Daniela Beltrami, Valeria Crepaldi, Veronica Redaelli, Giorgio Giaccone, Giuseppe Di Fede
Summary: Mutations in the PSEN1 gene are common causes of early-onset Alzheimer's disease. We report a novel PSEN1 mutation (I213S) found in an Italian patient with a family history of early-onset dementia. The patient experienced a gradual cognitive decline starting from the age of 40. Clinical and genetic studies suggest that this mutation may contribute to EOAD.
NEUROBIOLOGY OF AGING
(2022)
Review
Neurosciences
Gunnar Nordvall, Johan Lundkvist, Johan Sandin
Summary: Recent clinical data have shown that removing A beta-amyloid plaques in early Alzheimer's disease can slow down disease progression. This progress validates the amyloid cascade hypothesis and highlights the importance of targeting A beta-amyloid for therapeutic purposes. It also suggests that reducing the production of amyloidogenic A beta can prevent the formation of A beta-pathology. Further research is needed to explore the potential of gamma-secretase modulators in preventing and treating Alzheimer's disease.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Health Care Sciences & Services
Sujoita Sen, Logan Hallee, Chi Keung Lam
Summary: Heart diseases pose a major threat to human health globally, with a significant economic burden. The gamma-secretase enzyme is being studied as a potential therapeutic target for cardiac diseases, showing promise in maintaining cardiac function and potentially combating heart diseases.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Joo-Hee Lee, Na-Hyun Ahn, Su-Bin Choi, Youngeun Kwon, Seung-Hoon Yang
Summary: Alzheimer's disease is characterized by severe brain damage and dementia, with few effective therapeutics currently available. Modulation of abnormal amyloid beta aggregates formation is suggested as a key approach to treating the disease, by downregulating A beta peptides and suppressing their accumulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Neurosciences
Alvaro Miranda, Enrique Montiel, Henning Ulrich, Cristian Paz
Summary: Alzheimer's disease is characterized by cerebral cortex atrophy and accumulation of amyloid plaques. Current focus in treatment lies in reducing A beta production to slow down disease progression.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Clinical Neurology
Agnes A. Luty, John B. J. Kwok, Carol Dobson-Stone, Clement T. Loy, Kirsten G. Coupland, Helena Karlstrom, Tomasz Sobow, Joanna Tchorzewska, Aleksandra Maruszak, Maria Barcikowska, Peter K. Panegyres, Cezary Zekanowski, William S. Brooks, Kelly L. Williams, Ian P. Blair, Karen A. Mather, Perminder S. Sachdev, Glenda M. Halliday, Peter R. Schofield
ANNALS OF NEUROLOGY
(2010)
Article
Neurosciences
Louise Hedskog, Jesper Brohede, Birgitta Wiehager, Catarina Moreira Pinho, Priya Revathikumar, Lena Lilius, Elzbieta Glaser, Caroline Graff, Helena Karlstrom, Maria Ankarcrona
JOURNAL OF ALZHEIMERS DISEASE
(2012)
Article
Biochemistry & Molecular Biology
Johanna Wanngren, Jenny Franberg, Annelie I. Svensson, Hanna Laudon, Fredrik Olsson, Bengt Winblad, Frank Liu, Jan Naslund, Johan Lundkvist, Helena Karlstrom
JOURNAL OF BIOLOGICAL CHEMISTRY
(2010)
Article
Biochemistry & Molecular Biology
Annelie Pamren, Johanna Wanngren, Lars O. Tjernberg, Bengt Winblad, Ratan Bhat, Jan Naslund, Helena Karlstrom
JOURNAL OF BIOLOGICAL CHEMISTRY
(2011)
Article
Biochemistry & Molecular Biology
Johanna Wanngren, Jan Ottervald, Santiago Parpal, Erik Portelius, Kia Stromberg, Tomas Borgegard, Rebecka Klintenberg, Anders Jureus, Jenny Blomqvist, Kaj Blennow, Henrik Zetterberg, Johan Lundkvist, Susanne Rosqvist, Helena Karlstrom
JOURNAL OF BIOLOGICAL CHEMISTRY
(2012)
Article
Cell Biology
Louise Hedskog, Camilla A. Hansson Petersen, Annelie I. Svensson, Hedvig Welander, Lars O. Tjernberg, Helena Karlstrom, Maria Ankarcrona
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2011)
Article
Neurosciences
Tomas Borgegard, Susanne Gustavsson, Charlotte Nilsson, Santiago Parpal, Rebecka Klintenberg, Anna-Lena Berg, Susanne Rosqvist, Lutgarde Serneels, Samuel Svensson, Fredrik Olsson, Shaobo Jin, Hongmei Yan, Johanna Wanngren, Anders Jureus, Anna Ridderstad-Wollberg, Patrik Wollberg, Kenneth Stockling, Helena Karlstrom, Asa Malmberg, Johan Lund, Per I. Arvidsson, Bart De Strooper, Urban Lendahl, Johan Lundkvist
JOURNAL OF NEUROSCIENCE
(2012)
Article
Multidisciplinary Sciences
Jenny Franberg, Helena Karlstrom, Bengt Winblad, Lars O. Tjernberg, Susanne Frykman
Article
Multidisciplinary Sciences
Sophia Schedin-Weiss, Mitsuhiro Inoue, Yasuhiro Teranishi, Natsuko Goto Yamamoto, Helena Karlstrom, Bengt Winblad, Lars O. Tjernberg
Article
Biochemistry & Molecular Biology
Johanna Wanngren, Patricia Lara, Karin Ojemalm, Silvia Maioli, Nasim Moradi, Lu Chen, Lars O. Tjernberg, Johan Lundkvist, IngMarie Nilsson, Helena Karlstrom
Review
Biochemistry & Molecular Biology
Helena Karlstrom, William S. Brooks, John B. J. Kwok, G. Anthony Broe, Jillian J. Kril, Heather McCann, Glenda M. Halliday, Peter R. Schofield
JOURNAL OF NEUROCHEMISTRY
(2008)
Article
Neurosciences
Helena Karlstrom, John B. J. Kwok, Gillian C. Gregory, Marianne Hallupp, William S. Brooks, Peter R. Schofield
Article
Biochemistry & Molecular Biology
Nodi Dehvari, Angel Cedazo-Minguez, Ola Isacsson, Tatjana Nilsson, Bengt Winblad, Helena Karlstrom, Eirikur Benedikz, Richard F. Cowburn
JOURNAL OF NEUROCHEMISTRY
(2007)
Article
Developmental Biology
J Lundkvist, SW Zhu, EM Hansson, P Schweinhardt, Q Miao, P Beatus, K Dannaeus, H Karlstrom, CB Johansson, M Viitanen, B Rozell, C Spenger, A Mohammed, H Kalimo, U Lendahl
Article
Biochemistry & Molecular Biology
Soojung Hahn, Gyuri Kim, Sang-Man Jin, Jae Hyeon Kim
Summary: This study utilized three-dimensional intestinal organoids to investigate the effects of metformin on inflammatory bowel disease (IBD) and found that metformin can enhance intestinal barrier function and reduce levels of inflammatory cytokines.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
V. V. Sudarev, M. S. Gette, S. V. Bazhenov, O. M. Tilinova, E. V. Zinovev, I. V. Manukhov, A. I. Kuklin, Yu. L. Ryzhykau, A. V. Vlasov
Summary: This study investigated the self-assembly processes of ferritin-based protein complexes and obtained structurally characterized oligomeric states. These results provide new potential and opportunities for the application of ferritin in various fields.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Yalda Sabaghi, Farnaz Pourfarzad, Leila Zolghadr, Azita Bahrami, Tahereh Shojazadeh, Alireza Farasat, Nematollah Gheibi
Summary: p-Coumaric acid (p-CA) is a plant compound with anti-cancer activities. This study designed a nano-liposomal carrier containing p-CA to enhance its effectiveness against melanoma cells. The findings showed that the liposomal form of p-CA had a greater impact on the cells. Kinetic modeling indicated that the best fitting model was zero-order.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
M. D. Nazmul Hasan, Md Mahfuzur Rahman, Al Asmaul Husna, Nobuhiro Nozaki, Osamu Yamato, Naoki Miura
Summary: This study investigated the expression of ncRNAs other than miRNAs in different histologic subtypes of canine mammary gland tumors (MGT). Three aberrantly expressed ncRNAs were identified as potential biomarkers for differentiating MGT subtypes. YRNA and tRFs expression levels were found to be decreased in metastatic compared to primary MGT cell lines.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Seine A. Shintani
Summary: In this study, the researchers used signal analysis to study the instantaneous amplitude and phase of sarcomeric oscillations in skeletal muscle. They identified two types of oscillations, sarcomeric oscillations and sarcosynced oscillations, and visualized their behavior during propagating waves. The researchers discovered the presence of sarcomeric defect holes and sarcomeric collision holes, which are important indicators for understanding the oscillation properties of sarcomeres. This finding has important implications for improving our understanding of muscle function and its regulatory mechanisms.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Shuanglin Zhang, Yuzhong Jia, Guolan Ma, Yanyan Yang, Zhenzhen Cao, Antao Luo, Zefu Zhang, Shihan Li, Jie Wen, Hanfeng Liu, Jihua Ma
Summary: Bupleurum is an antiarrhythmic agent that may exert its effects by inhibiting L-type calcium channels.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Tomotaka Ohkubo, Yasuhiko Matsumoto, Hiroaki Sasaki, Kaoru Kinoshita, Yuki Ogasawara, Takashi Sugita
Summary: This study found that Citrobacter koseri inhibits the growth of Staphylococcus epidermidis, disrupting the balance between S. epidermidis and Staphylococcus aureus, and exacerbating inflammation in atopic dermatitis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Toshifumi Asano, Philipp Sasse, Takao Nakata
Summary: A Cre recombination-based fluorescent reporter system was developed to monitor cell-cell fusion. The system successfully detected the formation of multinuclear myotubes and placental syncytiotrophoblast. This tool could facilitate the study of cell-to-cell fusion.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Ke Shi, Yunlong Shan, Xiao Sun, Kuida Chen, Qiong Luo, Qiang Xu
Summary: This study found that low expression of TP53INP2 is associated with poor survival in colorectal cancer (CRC) patients. As the malignancy of CRC progresses, TP53INP2 expression gradually decreases. Knockdown of TP53INP2 promotes CRC cell proliferation and tumor growth. Mechanistically, TP53INP2 deficiency decreases phosphorylation of beta-catenin, leading to increased accumulation and enhanced nuclear translocation and transcriptional activity. Additionally, TP53INP2 sequesters TIM50, inhibiting its activation of beta-catenin. In conclusion, downregulation of TP53INP2 promotes CRC progression by activating beta-catenin.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Martina Rossi, Fabio Tomaselli, Alejandro Hochkoeppler
Summary: Oligomeric enzymes are known for their higher catalytic rates compared to monomeric enzymes, but the extent of additivity in their activity is still not well understood. This study used tetrameric rabbit lactate dehydrogenase as a model to examine the kinetics of its catalytic action. Surprisingly, when the concentration of the limiting reactant exceeded that of a single subunit, there was a significant slowdown in the enzyme's conformational rearrangements.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Amin Sahraei, Mohammad Javad Shamsoddini, Fakhrossadat Mohammadi, Leila Hassani
Summary: This study explored the inhibitory effects of gallium curcumin, indium curcumin, and vanadyl curcumin on the amyloid fibrillation of hen egg white lysozyme, as well as the binding interactions of these metal complexes with the enzyme. The results showed that indium curcumin and vanadyl curcumin exhibited higher binding affinities and stronger inhibitory effects on amyloid fibrillation compared to gallium curcumin.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Takahiro Sasaki, Yoshiki Kuse, Shinsuke Nakamura, Masamitsu Shimazawa
Summary: PGRN deficiency plays a significant role in cardiac remodeling and arrhythmias post-myocardial infarction (MI), potentially by promoting metabolic abnormalities in macrophages.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Hongwei Zhao, Yiqiang Li, Yibo Zhang, Chi Zhang
Summary: Electrical brain stimulation technology is commonly used to treat brain neurological disorders, but it can cause side effects. This study investigated the impact of electric fields on nerve fibers and revealed the possible origin of side effects. The findings provide guidance for selecting electrical parameters in clinical stimulation therapy.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Julia S. Scott, Lake-Ee Quek, Andrew J. Hoy, Johannes V. Swinnen, Zeyad D. Nassar, Lisa M. Butler
Summary: The fatty acid elongation enzyme ELOVL5 plays a critical role in promoting metastasis in prostate cancer. Knocking down ELOVL5 leads to the accumulation of malonyl-CoA, which inhibits fatty acid oxidation in mitochondria. This study highlights the importance of fatty acid elongation in regulating cell viability and provides a potential target for prostate cancer treatment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Zan Zhou, Wen-jun Jiang, Li Li, Jun-qiang Si
Summary: This study investigates the effect of noise exposure on cognitive function in mice and explores the underlying molecular mechanisms. The findings suggest that noise exposure leads to increased inflammation, increased phosphorylation of Tau protein, and decreased levels of postsynaptic density protein, resulting in cognitive impairment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)