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
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
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
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
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
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
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.
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)
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
Biochemistry & Molecular Biology
Siling Liu, Zhongyu Zhang, Lianwei Li, Li Yao, Zhanshan Ma, Jiali Li
Summary: PTPRT is downregulated in the brains of AD patients and mouse models, and its cleavage releases PICD which translocates to the nucleus and inhibits pSTAT3 accumulation, leading to neuronal cell death. Overexpression of PICD affects gene expression related to synapse formation, cell adhesion, and protein dephosphorylation. Furthermore, PICD overexpression improves synaptic function, reduces phospho-STAT3(Y705) and amyloid beta production in APP/PS1 mice, and partially rescues behavioral deficits.
Article
Neurosciences
Carlos M. Soto-Faguas, Paula Sanchez-Molina, Carlos A. Saura
Summary: Mutations in presenilin genes accelerate amyloid-beta and tau pathologies in Alzheimer's disease. PS deficiency in mice leads to brain atrophy, inflammation, and accumulation of pathological tau. Inactivating PS genes exacerbates memory deficits in Tau transgenic mice by accelerating tau phosphorylation and aggregation. Tau aggregation and phosphorylation play key roles in neurodegeneration linked to familial AD.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Hikari Watanabe, Chika Yoshida, Masafumi Hidaka, Tomohisa Ogawa, Taisuke Tomita, Eugene Futai
Summary: Through studying Aph1 mutations and using a yeast gamma-secretase assay, we found that the L30F/T164A mutation can activate gamma-secretase activity, leading to increased production of Aβ in mouse embryonic fibroblasts without apparent modulatory function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Bruno P. Imbimbo, Stefania Ippati, Mark Watling, Camillo Imbimbo
Summary: According to the beta-amyloid (A beta) hypothesis, brain A beta accumulation is the primary cause of cognitive deficit and dementia in Alzheimer's disease (AD). While many anti-A beta drugs have failed in clinical trials, recent studies have shown encouraging results for antibodies that clear amyloid plaques. These findings suggest that decreased levels of soluble monomeric A beta may be the main driver of AD, rather than the aggregated forms.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Ryota Suzuki, Haruka Takahashi, Chika Yoshida, Masafumi Hidaka, Tomohisa Ogawa, Eugene Futai
Summary: In this study, the APP mutation T714I, which is associated with familial Alzheimer's disease, was found to severely reduce the cleavage of A beta. Secondary mutations were identified that restored the cleavage of APP T714I and could modulate the production of A beta species in mammalian cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Neurosciences
Yee Jie Yeap, Nagaendran Kandiah, Dean Nizetic, Kah-Leong Lim
Summary: Alzheimer's disease (AD) is the most common cause of dementia, affecting millions of elderly individuals worldwide. Despite extensive research, the cause of AD remains controversial and there is currently no cure. However, recent studies have identified the protease BACE2 as a potential therapeutic target for AD due to its non-amyloidogenic role in preventing the generation of toxic amyloid-beta peptides. This review discusses emerging evidence supporting the neuroprotective role of BACE2 in AD and provides an update on the identification of gene mutations linked to increased risk and earlier disease onset.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Microbiology
Jaime A. Bibian-Garcia, Jorge A. Ortiz-Ramirez, Lilia M. Almanza-Villegas, R. Aguayo-Ortiz, C. Cano-Canchola, Mayra Cuellar-Cruz, Everardo Lopez-Romero
Summary: Candida albicans is a common fungal pathogen in humans, particularly in immunocompromised patients. This study investigates the mechanisms of glycoprotein assembly in the organism and identifies a bifunctional nucleotidase that plays a role in maintaining the balance of sugar donors during the glycosylation process.
ANTONIE VAN LEEUWENHOEK INTERNATIONAL JOURNAL OF GENERAL AND MOLECULAR MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Andy Y. Liu, Rodrigo Aguayo-Ortiz, Guadalupe Guerrero-Serna, Nulang Wang, Muriel G. Blin, Daniel R. Goldstein, L. Michel Espinoza-Fonseca
Summary: This study investigated the molecular architecture of phospholamban (PLN) and sarcolipin (SLN) oligomers through molecular dynamics simulations and Western blot analysis. The results revealed that PLN mainly forms a pentamer, while SLN primarily exists as dimers and trimers in the membrane. These distinct oligomeric states may contribute to tissue-specific SERCA regulation.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Rodrigo Aguayo-Ortiz, Dulce C. Guzman-Ocampo, Laura Dominguez
Summary: This study identifies the binding site of flavonoid morin (MOR) on human gamma D-crystallin (H gamma DC) and confirms its stabilizing effect on the structure of H gamma DC. This is of significant importance for the discovery of new H gamma DC aggregation inhibitors.
BIOPHYSICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Rodrigo Aguayo-Ortiz, Laura Dominguez
Summary: Dinitroaniline derivatives are widely used as herbicides and exhibit good antiparasitic activity against protozoan parasites. Oryzalin, a representative dinitroaniline derivative, inhibits the growth of Toxoplasma gondii by binding selectively to alpha-tubulin and inhibiting microtubule polymerization.
Article
Biochemistry & Molecular Biology
Jessi J. Bak, Rodrigo Aguayo-Ortiz, Nishadh Rathod, Joseph O. Primeau, Muhammad Bashir Khan, Seth L. Robia, M. Joanne Lemieux, Michel L. Espinoza-Fonseca, Howard S. Young
Summary: Intracellular calcium signaling is crucial for all life forms, with SERCA playing a vital role in maintaining calcium homeostasis. Tissue-specific transmembrane subunits like phospholamban and sarcolipin regulate SERCA in higher organisms, but the recent discovery of arthropod sarcolambans expands the evolutionary divergence in calcium pump regulatory subunits. Recombinant sarcolamban peptides from different arthropods were found to be superinhibitors of SERCA, showing either phospholamban-like or sarcolipin-like characteristics, revealing novel insights into SERCA regulation.
Article
Biochemical Research Methods
Guillermo Goode-Romero, Laura Dominguez
Summary: The CX3CR1 receptor and its ligand fractalkine play a critical role in various cellular pathways and diseases. This study used MD simulations to investigate the receptor's conformation and ligand interactions, aiming to understand its functional states and the complexity of the GPCR superfamily.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2022)
Article
Biochemistry & Molecular Biology
Carlos D. Flores-Leon, Laura Dominguez, Rodrigo Aguayo-Ortiz
Summary: In this study, alchemical free energy methods and molecular dynamics simulations were used to investigate the impact of ORY resistance mutations on the interaction between TgAT and ORY. The results suggest that the mutations decrease the affinity of ORY to TgAT and reduce TgAT's flexibility and stability, resulting in the closure of the ORY binding site.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Multidisciplinary Sciences
Guillermo Goode-Romero, Laura Dominguez
Summary: This study characterized the structural features and mechanistic processes of the CCR5 receptor using atomistic molecular dynamics simulations. The findings provide insights into the role of CCR5 in various diseases and contribute to the development of pharmacological interventions.
Article
Biochemistry & Molecular Biology
Dulce C. Guzman-Ocampo, Rodrigo Aguayo-Ortiz, Jose-Luis Velasco-Bolom, Pancham Lal Gupta, Adrian E. Roitberg, Laura Dominguez
Summary: y-Secretase (GS) is an intramembrane aspartyl protease that plays a crucial role in the generation of different isoforms of amyloid-β (Aβ) peptides, which are associated with Alzheimer's disease. Through pH-REMD simulations, we discovered that the catalytic dyad of GS is deprotonated in its apo form at physiological pH, but the presence of substrate shifts its protonation state towards physiological pH. Our study provides valuable mechanistic insights into the GS mechanism and its potential role in the development of Alzheimer's disease.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Jose-Luis Velasco-Bolom, Laura Dominguez
Summary: Previous studies suggest that genetic mutations and post-translational modifications play a role in cataract formation. This study used molecular dynamics simulations to evaluate the structural changes in the beta B2-crystallin protein, uncovering important insights into the initial steps of cataract formation.
BIOPHYSICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Carlos Martinez-Conde, Blanca Colin-Lozano, Abraham Gutierrez-Hernandez, Emanuel Hernandez-Nunez, Lilian Yepez-Mulia, Luis Fernando Colorado-Pablo, Rodrigo Aguayo-Ortiz, Jaime Escalante, Julio C. Rivera-Leyva, Jessica Nayelli Sanchez-Carranza, Elizabeth Barbosa-Cabrera, Gabriel Navarrete-Vazquez
Summary: In this study, a rational design strategy was used to synthesize retroalbendazole (RetroABZ) as a potential therapeutic compound for giardiasis. RetroABZ exhibited enhanced in vitro activity against Giardia lamblia and improved water solubility compared to albendazole. Molecular docking and dynamics studies supported the higher affinity of RetroABZ towards the target protein tubulin. Overall, RetroABZ shows promise as a therapeutic candidate for giardiasis and other parasitic diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Siva Santhiya Arul, Brinda Balakrishnan, Savithri S. Handanahal, Sangita Venkataraman
Summary: Viral nanoparticles are self-assembling delivery systems used for vaccines and therapeutic agents. They have improved biocompatibility and are widely used in various biomedical applications. However, large-scale production of VNPs still faces challenges.
Article
Biochemistry & Molecular Biology
Wisely Chua, Carl O. Marsh, Si En Poh, Winston LC. Koh, Melody Li Ying Lee, Li Fang Koh, Xin-Zi Emily Tang, Peter See, Zheng Ser, Shi Mei Wang, Radoslaw M. Sobota, Thomas L. Dawson Jr, Yik Weng Yew, Steven Thng, Anthony J. O'Donoghue, Hazel H. Oon, John E. Common, Hao Li
Summary: In this study, the gene expression of enzymes secreted by Malassezia globosa in the skin was investigated using targeted RNA sequencing. The study found that the expression of these enzymes is regulated by the fungus's environment and differs significantly from healthy skin sites. Additionally, a pseudoprotease MGL_3331 was identified to elicit an immune reaction in patients with atopic dermatitis. This highlights the importance of studying fungal proteins in physiologically relevant environments and their role in host immunity.
Article
Biochemistry & Molecular Biology
Belisa Parmeggiani, Marian Flores Signori, Cristiane Cecatto, Marina Rocha Frusciante, Manuela Bianchin Marcuzzo, Debora Guerini Souza, Rafael Teixeira Ribeiro, Bianca Seminotti, Diogo Onofre Gomes de Souza, Cesar Augusto Joa o Ribeiro, Moacir Wajner, Guilhian Leipnitz
Summary: Non ketotic hyperglycinemia (NKH) is a disorder caused by mutations in the genes encoding glycine cleavage system proteins, leading to severe neurodegeneration and white matter alterations. The study found that glycine affects myelin structure, glutamatergic system, and induces oxidative stress in neonatal rats and MO3.13 oligodendroglial cells.
Review
Biochemistry & Molecular Biology
Marie Rose Ndella Thiaw, Pascal Gantet
Summary: Mini zinc fingers play important roles in plant development, including control of cell division and expansion, meristem state transition, and growth and organ development. They have diverse modes of action, such as direct gene activation, interaction with specific transcription factors, and aggregation of protein complexes for chromatin remodeling. Further research is needed to explore their wider range of biological functions and their involvement in biotic and abiotic stress responses.
Article
Biochemistry & Molecular Biology
Shao-Jui Lai, Takahiro Kameda, Maasa Morita, Yuka Yamagata, Kaoruko Nishizaka, Yuna Horiuchi, Yukihiro Kobayashi, Yoko Usami, Jun-Jen Liu, Takeshi Kasama, Minoru Tozuka, Ryunosuke Ohkawa
Summary: In this study, the co-modification and impact of chymase and MPO on HDL were investigated. Sequential treatment with MPO and chymase generated two novel apoA-I fragments from HDL, one of which has a specific immunological property and can be used to predict patients with normal HDL-C levels and cardiovascular diseases.
Article
Biochemistry & Molecular Biology
Xiao-Mi Sun, Asami Yoshida, Takuya Ishii, Yan-Rong Jiang, Yi-Li Gao, Mikinori Ueno, Katsuya Hirasaka, Kiyoshi Osatomi
Summary: This study found that infection with the causative bacteria of edwardsiellosis, Edwardsiella tarda NUF251, leads to the production of superoxide radicals, causing oxidative stress. The research on the Jfsod1 gene suggests that the transcription factor NF-IL6 plays a significant role in upregulating the transcriptional activity of the gene in response to oxidative stress induced by NUF251 infection.
Article
Biochemistry & Molecular Biology
Shane M. Carey, Sean P. Kearns, Matthew E. Millington, Gregory S. Buechner, Beda E. Alvarez Jr, Leily Daneshian, Brendan Abiskaroon, Maksymilian Chruszcz, Edward L. D'Antonio
Summary: The importance of F337 in TcGlcK was investigated using the hole mutagenesis approach, revealing its key interactions with aromatic tail groups in inhibitor molecules. Mutants retaining activity and structural similarity were obtained, suggesting the possibility of TcHxK existing as a monomer lacking the F337 residue. Similar D-glucosamine inhibitors may bind less strongly to TcHxK due to the absence of van der Waals contacts from residue side chains.
Article
Biochemistry & Molecular Biology
Catia Barria, Diogo Athayde, Guillem Hernandez, Leonor Fonseca, Jorge Casinhas, Tiago N. Cordeiro, Margarida Archer, Cecilia M. Arraiano, Jose A. Brito, Rute G. Matos
Summary: Ribonucleases play a crucial role in RNA regulation by processing, degrading, and quality controlling cellular transcripts. Campylobacter jejuni, the main cause of human gastroenteritis, relies on the exoribonuclease PNPase (CjPNP) for low-temperature survival, virulence factor synthesis, and swimming, cell adhesion/invasion, and chick colonization abilities. The crystallographic structure of CjPNP, along with SAXS analysis, confirms its trimeric arrangement and provides insight into domain arrangement and flexibility. Mutations in highly conserved residues reveal unexpected RNA degradation activity even under conditions favoring polymerization. These findings have significant implications for the development of strategies to combat C. jejuni infections.
Article
Biochemistry & Molecular Biology
Elvira R. Shaykhutdinova, Maria S. Severyukhina, Inna V. Kholoshenko, Elena A. Gondarenko, Irina V. Shelukhina, Elena V. Kryukova, Alina M. Ismailova, Elena S. Sadovnikova, Igor A. Dyachenko, Arkady N. Murashev, Victor I. Tsetlin, Yuri N. Utkin
Summary: Evidence suggests that activating nicotinic acetylcholine receptors (nAChRs) can reduce cardiac injury caused by ischemia and reperfusion. In this study, the expression of a4, a6, and a132 nAChR subunits in the rat heart's left ventricle was demonstrated. The nAChR agonists cytisine and varenicline, commonly used for nicotine addiction treatment, were found to significantly reduce myocardial ischemia-reperfusion injury, with varenicline showing greater protection. The presence of a4132, a7, and/or a6132-containing receptors suggests that the protective effect of varenicline may be mediated by these subunits. These findings indicate a potential new use for cytisine and varenicline as cardioprotective agents.
Article
Biochemistry & Molecular Biology
Xinhai Xiong, Wenjie Chen, Cheng Chen, Qi Wu, Chaopeng He
Summary: This article summarizes the important roles of Cx43 in disease development from the perspective of subcellular localization and provides new ideas for Cx43 as a therapeutic target and the search for related pathological mechanisms.
Article
Biochemistry & Molecular Biology
Veronica Bastos, Simone Pascoal, Kamila Lopes, Marcia Mortari, Helena Oliveira
Summary: Cancer, especially melanoma, is a major global health problem due to its metastatic capacity, treatment resistance, and high mortality rates. The Chartergellus-CP1 peptide isolated from Chartergellus communis wasp venom showed selective cytotoxicity towards melanoma cell lines, inducing apoptosis, cell cycle impairment, and intracellular ROS increase.
Article
Biochemistry & Molecular Biology
Charlotte Claeyssen, Nathan Bulangalire, Bruno Bastide, Onnik Agbulut, Caroline Cieniewski-Bernard
Summary: Maintenance of striated muscle tissue relies on a dynamic network of protein-protein interactions. Desmin intermediate filaments play a crucial role in heart and skeletal muscle by maintaining cell structure and contributing to various cellular processes. The assembly of desmin intermediate filaments requires aB-crystallin, which is involved in multiple cellular functions.
Article
Biochemistry & Molecular Biology
Dhritiman Dey, Adhiraj Dasgupta, Dipanjan Ghosh, Oindrila Bhattacharjee, Abhrajyoti Ghosh, Ayae Honda, Dhrubajyoti Chattopadhyay
Summary: This study successfully identified host factors that interact with Chandipura Virus (CHPV) and play a critical role in infection, including A2M, LRP1, and GRP78. Knocking out A2M has a severe effect on viral infection, indicating the potential role of these host proteins in viral entry into host cells.
Article
Biochemistry & Molecular Biology
Anna Dotsenko, Igor Sinelnikov, Aleksandra Rozhkova, Ivan Zorov, Arkady Sinitsyn
Summary: Xylanases play important roles in various industrial applications, such as feed additives, pulp and paper bleaching, and the production of bread, food, and drinks. Xylanases from the GH10 family show high thermostability and resistance to protein inhibitors, making them promising candidates for these processes. This study successfully improved the thermostability and enzymatic activity of GH10 xylanase, which could enhance its effectiveness as a feed additive and during pulp and paper bleaching.
Article
Biochemistry & Molecular Biology
M. Jaquet, M. Bengue, K. Lambert, G. Carnac, D. Misse, C. Bisbal
Summary: Changes to our environment have led to the emergence of human pathogens such as chikungunya virus, which is now a major public health concern. In this study, the interconnection between skeletal muscle cells metabolism, their differentiation stage, and the infectivity of chikungunya virus was investigated. The results showed that chikungunya virus infectivity is dependent on cell differentiation and metabolism and that the virus interferes with cellular metabolism.
