Review
Biochemistry & Molecular Biology
Mariana J. do Amaral, Maria Heloisa O. Freire, Marcius S. Almeida, Anderson S. Pinheiro, Yraima Cordeiro
Summary: Abnormal phase transitions are implicated in proteinopathies. Disordered proteins with nucleic acid-binding ability can drive the formation of reversible condensates, controlling nucleic acid processing/transport. The prion protein (PrP), although not a classical nucleic acid-binding protein, has properties similar to bona fide drivers of phase transitions. This article discusses recent studies and evidence supporting PrP phase transitions, emphasizing the central role of liquid-liquid phase separation (LLPS) in PrP physiology and pathology. The interaction of PrP with different ligands, including proteins and nucleic acids, is also explored, highlighting its potential role in prion disease pathogenesis. Therapeutic strategies targeting non-functional phase separation for the treatment of prion diseases and protein misfolding disorders are also discussed.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Essa M. Saied, Christoph Arenz
Summary: Sphingolipids are a class of compounds ubiquitous in eukaryotic plasma membranes, playing important roles in human and animal physiology and disease. Research into these 'Sphinx' lipids is hindered by their low concentrations and the lack of suitable standards, highlighting the need for the development of efficient and facile synthesis methods.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jing Li, Kenneth A. Satyshur, Lian-Wang Guo, Arnold E. Ruoho
Summary: Both bioactive sphingolipids and Sigma-1 receptor (S1R) chaperones are widely present in mammalian cell membranes. Endogenous compounds that regulate the S1R play an important role in controlling S1R responses to cellular stress. This study investigated the interaction between S1R and sphingosine (SPH) and N,N'-dimethylsphingosine (DMS) in intact Retinal Pigment Epithelial cells (ARPE-19) and suggested that SPH and DMS are endogenous S1R agonists. Molecular docking analysis showed strong interactions between SPH/DMS and specific residues in the S1R, indicating a membrane bilayer pathway for SPH/DMS to access the S1R beta barrel. The enzymatic control of ceramide concentrations in intracellular membranes may dictate the availability of SPH and DMS to S1R and subsequently regulate S1R activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Fei Meng, Naitong Sun, Dongyan Liu, Jia Jia, Jun Xiao, Haiming Dai
Summary: BCL2L13, a BCL2-like protein, has been found to play important roles in both physiological and pathological processes, not only showing pro-apoptotic activity but also influencing cell death and mitophagy.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biology
Emily J. Zaniker, Elnur Babayev, Francesca E. Duncan
Summary: Ovulation is a fundamental biological event that involves the rupture of follicle wall and release of mature egg. This process is driven by proteolytic and inflammatory pathways, as well as structural alterations to the vasculature and cavity of the follicle. Comparisons with other rupture events, such as intracranial aneurysms and chorioamniotic membrane rupture, reveal common processes and differentially expressed genes. Understanding the physiology of ovulation through analysis of transcriptomic data and experimental techniques from studies of rupture in other biological systems can provide insights for future studies and novel targets in the field of reproductive biology.
BIOLOGICAL REVIEWS
(2023)
Review
Endocrinology & Metabolism
Yong Geun Jeon, Ye Young Kim, Gung Lee, Jae Bum Kim
Summary: Lipids are essential metabolites that serve as energy sources, structural components, and signaling mediators. Lipogenesis plays a crucial role in metabolic, immune, and nervous systems, and abnormal lipogenesis can lead to various diseases. This review discusses the regulatory mechanisms, physiological roles, pathological importance, and therapeutic implications of lipogenesis in different tissues.
Review
Cell & Tissue Engineering
Alaina Cockerell, Liam Wright, Anish Dattani, Ge Guo, Austin Smith, Krasimira Tsaneva-Atanasova, David M. Richards
Summary: Embryo development is a critical stage in the life cycle of many organisms, but the earliest stages of mammalian embryogenesis are still poorly understood. This is due to a lack of high-resolution spatial and temporal data, limited use of model organisms, and a lack of interdisciplinary approaches. This review explains the theoretical frameworks and biophysical processes for modeling mammalian embryos, summarizes previous models, and discusses future research directions.
Article
Biochemical Research Methods
Jing Zhao, Lipeng Qiao, Yu Xia
Summary: In this study, a MS/MS method based on CID-triggered RDD was developed to characterize sphingoid bases in depth. By applying this method in experiments, the structural diversity of sphingoid bases and novel variations in sphingolipid metabolism were revealed.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Review
Immunology
Philippe Rascle, Griffin Woolley, Stephanie Jost, Cordelia Manickam, R. Keith Reeves
Summary: Natural killer (NK) cells play a critical role in defending against viral infections and cancers. The balance between activating and inhibitory NK cell receptors determines the overall NK cell response. NK cell education, which is influenced by factors such as self-major histocompatibility complex class I (MHC-I) molecules and inhibitory KIR expression, is crucial in generating tuned effector NK cell responses in different diseases. This review discusses the relationship between NK cell education and various physiological factors, as well as the diverse effector functions of educated NK cells in different pathologies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Applied
Ai Suzuki-Iwashima, Ai Iwasawa, Mayumi Kawai, Hiroaki Kubouchi, Ryuhei Ozaki, Kazuo Miyashita, Makoto Shiota
Summary: The study demonstrated that milk SPGs extracted from butter serum inhibited the oxidation of fish oil TAG more effectively than a standard SPG (d18:1), and the reaction products from d18:0 showed stronger antioxidant activity than those from d18:1, suggesting that d18:0 may be a significant factor contributing to the difference in antioxidant activity between milk SPGs and d18:1.
Article
Biochemistry & Molecular Biology
Hassan Melhem, Daniel Regan-Komito, Jan Hendrik Niess
Summary: Maintaining intestinal health requires a clear segregation between epithelial cells and luminal microbes, which is achieved by the intestinal mucus layer produced by goblet cells. Disruption of goblet cells and mucus layer dysfunction are closely related to the pathogenesis of inflammatory bowel disease (IBD), but the molecular mechanisms regulating goblet cell physiology and the mucus layer remain unclear. Further research is needed to understand how internal (host) and external (diets and bacteria) factors modulate the mucus layer and its impact on the onset of IBD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Pavel P. Tregub, Anton S. Averchuk, Tatyana Baranich, Maria Ryazanova, Alla B. Salmina
Summary: The remodeling of cerebral microvessels has a significant impact on brain plasticity and neurodegenerative diseases. Abnormal neoangiogenesis and microvascular regression are associated with blood-brain barrier breakdown, neuroinflammation, and dysfunction of the neurovascular unit. This review summarizes the mechanisms of blood vessel regression and pruning, and discusses novel approaches to modulating cerebral remodeling and preventing aberrant microvascular activity in chronic neurodegeneration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Daisuke Mikami, Shota Sakai, Megumi Nishimukai, Kohei Yuyama, Katsuyuki Mukai, Yasuyuki Igarashi
Summary: This study revealed that the structural differences among LCBs, particularly geometric isomerism at the C8-C9 position, significantly affected the absorption percentages and ratio of metabolites. It is the first report to elucidate that the absorption and metabolism of sphingolipids are dependent on their LCB structure. These findings could be utilized for developing functional foods that are more readily absorbed.
LIPIDS IN HEALTH AND DISEASE
(2021)
Review
Medicine, General & Internal
Juan Wang, Wenkang Wang, Hui Wang, Biguang Tuo
Summary: The Solute Carrier Family 26 (SLC26) is a versatile anion transporter family with diverse functions in mammalian organs, with SLC26A6 playing a particularly crucial role in ion homeostasis and acid-base balance. Research on the role of SLC26A6 in various diseases has been increasing in recent years, highlighting its significance in intestinal and pancreatic diseases, nephrolithiasis, fetal skeletal dysplasia, and arrhythmia.
FRONTIERS IN MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Haobo Li, Lena E. Trager, Xiaojun Liu, Margaret H. Hastings, Chunyang Xiao, Justin Guerra, Samantha To, Guoping Li, Ashish Yeri, Rodosthenis Rodosthenous, Michael G. Silverman, Saumya Das, Amrut V. Ambardekar, Michael R. Bristow, Juan Manuel Gonzalez-Rosa, Anthony Rosenzweig
Summary: This study identifies a novel pathway, lncExACT1-DCHS2, that regulates cardiac hypertrophy and cardiomyogenesis. lncExACT1-DCHS2 acts as a master switch toggling the heart between physiological and pathological growth to determine functional outcomes, providing a potentially tractable therapeutic target for harnessing the beneficial effects of exercise.
Article
Biochemistry & Molecular Biology
Sarka Pokorna, Ana E. Ventura, Tania C. B. Santos, Martin Hof, Manuel Prieto, Anthony H. Futerman, Liana C. Silva
Summary: This study provides a thorough analysis of the factors that can lead to variability in Laurdan GP measurements and suggests approaches to improve data quality. It also demonstrates the impact of cell culture conditions on GP determination.
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Joaquim Trigo Marques, Catarina Frazao De Faria, Marina Reis, Diana Machado, Susana Santos, Maria da Soledade Santos, Miguel Viveiros, Filomena Martins, Rodrigo F. M. De Almeida
Summary: The increase in multidrug-resistant tuberculosis has made the challenge of ending this epidemic by 2030 even tougher. This has led to a search for more efficient antitubercular compounds, with a focus on isoniazid derivatives in this study. The study evaluates the cytotoxicity, binding to human serum albumin, and activity against resistant strains of Mycobacterium tuberculosis of these derivatives, showing promising results for their potential use as improved treatments.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Tania C. B. Santos, Tamir Dingjan, Anthony H. Futerman
Summary: This article discusses the complexity of lipid synthesis in modern cell membranes, specifically focusing on sphingolipids (SLs). The authors introduce the concept of the 'anteome', which describes the network of metabolic pathways that must have evolved to allow for the synthesis of SLs. They also suggest that current models of life origins and evolution lack sufficient experimental evidence to explain the appearance of this complex metabolic pathway and its anteome.
Article
Biochemistry & Molecular Biology
Orsolya Domotor, Ricardo G. Teixeira, Gabriella Spengler, Fernando Avecilla, Fernanda Marques, Oscar A. Lenis-Rojas, Cristina P. Matos, Rodrigo F. M. de Almeida, Eva A. Enyedy, Ana Isabel Tomaz
Summary: In this study, two Ru(II)-polypyridyl compounds were prepared and characterized. The solid-state structure was confirmed by X-ray diffraction analysis. The solubility, stability, and lipophilicity of the complexes were investigated under physiological mimetic conditions, as well as their potential uptake by passive diffusion. The complexes exhibited cytotoxicity on ovarian and colon cancer cells and induced late apoptosis and necrosis. They showed weak binding to human serum albumin but significant binding to calf thymus DNA.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Nuno Martinho, Joaquim M. T. Marques, Iryna Todoriko, Manuel Prieto, Rodrigo F. M. de Almeida, Liana C. Silva
Summary: Increasing evidence suggests that lipids play a critical role in the toxicity and resistance mechanisms of platinum(II) complexes. This study investigated the ability of cisplatin and its cationic species to induce phase changes in model membranes with different lipid compositions. The results showed that the effect of platinum(II) complexes on membrane fluidity depends on the lipid composition and properties, and that high concentrations of these complexes can alter the permeability of lipid membranes without inducing collapse or aggregation.
MOLECULAR PHARMACEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Radoslaw Starosta, Telma C. Santos, Andreia F. Dinis F. de Sousa, Maria Soledade Santos, M. Luisa Corvo, Ana Isabel Tomaz, Rodrigo F. M. de Almeida
Summary: This study investigates the possible role of the cell membrane in the mechanism of action of two ruthenium complexes against human tumor cells. The results show that these complexes increase the permeability of lipid vesicles and alter the biophysical properties of the membranes. Moreover, the effects of the complexes depend on changes in membrane lipid composition.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Museer A. Lone, Sen Zeng, Florence Bourquin, Mengli Wang, Shunxiang Huang, Zhiqiang Lin, Beisha Tang, Ruxu Zhang, Thorsten Hornemann
Summary: This study reports a novel SPTLC1p.L38R mutation in a young Chinese girl with juvenile ALS. The mutation interferes with the interaction between the protein and the regulatory ORMDL subunit of SPT, leading to increased sphingolipid synthesis, particularly dihydro-sphingolipids. These findings suggest a potential link between SPTLC1-ALS mutations and neurotoxicity.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2023)
Article
Biochemistry & Molecular Biology
Ana E. Ventura, Sarka Pokorna, Natalie Huhn, Tania C. B. Santos, Manuel Prieto, Anthony H. Futerman, Liana C. Silva
Summary: This study demonstrates the use of Laurdan as a fluorescent probe to label and characterize changes in cellular lipid droplets (LD). The composition of LD and various cellular and environmental factors affect the biophysical properties of LD. The findings suggest that the specific alterations in LD properties might play a role in LD pathophysiology and metabolism.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2023)
Article
Biochemistry & Molecular Biology
Andres Alguacil, Franco Scalambra, Antonio Romerosa, Andreia Bento-Oliveira, Fernanda Marques, Ines Maximiano, Rodrigo F. M. de Almeida, Ana Isabel Tomaz, Andreia Valente
Summary: The cytotoxic activity of a series of piano-stool-{CpRu} complexes containing different ligands against breast cancer cells was evaluated, and their mechanism of action and ruthenium uptake were studied. Two new piano-stool-{CpRu} complexes were synthesized and characterized, and their catalytic properties were investigated.
BIOINORGANIC CHEMISTRY AND APPLICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Tania C. B. Santos, Anthony H. Futerman
Summary: Lipids play a crucial role in the origin of life, but current experimental approaches have limitations in determining their mechanistic insights. More nuanced experimental methods are needed to understand the generation and function of lipids in the origin of life.
PROGRESS IN LIPID RESEARCH
(2023)
Article
Medicine, Research & Experimental
Charlotte Gehin, Museer A. Lone, Winston Lee, Laura Capolupo, Sylvia Ho, Adekemi M. Adeyemi, Erica H. Gerkes, Alexander P. A. Stegmann, Estrella Lopez-Martin, Eva Bermejo-Sanchez, Beatriz Martinez-Delgado, Christiane Zweier, Cornelia Kraus, Bernt Popp, Vincent Strehlow, Daniel Graefe, Ina Knerr, Eppie R. Jones, Stefano Zamuner, Luciano A. Abriata, Vidya Kunnathully, Brandon E. Moeller, Anthony Vocat, Samuel Rommelaere, Jean-Philippe Bocquete, Evelyne Ruchti, Greta Limoni, Marine Van Campenhoudt, Samuel Bourgeat, Petra Henklein, Christian Gilissen, Bregje W. van Bon, Rolph Pfundt, Marjolein H. Willemsen, Jolanda H. Schieving, Emanuela Leonardi, Fiorenza Soli, Alessandra Murgia, Hui Guo, Qiumeng Zhang, Kun Xia, Christina R. Fagerberg, Christoph P. Beier, Martin J. Larsen, Irene Valenzuela, Paula Fernandez-alvarez, Shiyi Xiong, Robert Smigiel, Vanesa Lopez-Gonzalez, Lluis Armengol, Manuela Morleo, Angelo Selicorni, Annalaura Torella, Moira Blyth, Nicola S. Cooper, Valerie Wilson, Renske Oegema, Yvan Herenger, Aurore Garde, Ange-Line Bruel, Frederic Tran Mau-Them, Alexis B. R. Maddocks, Jennifer M. Bain, Musadiq A. Bhat, Gregory Costain, Peter Kannu, Ashish Marwaha, Neena L. Champaigne, Michael J. Friez, Ellen B. Richardson, Vykuntaraju K. Gowda, Varunvenkat M. Srinivasan, Yask Gupta, Tze Y. Lim, Simone Sanna-Cherchi, Bruno Lemaitre, Toshiyuki Yamaji, Kentaro Hanada, John E. Burke, Ana Marjia Jaksic, Brian D. McCabe, Paolo De Los Rios, Thorsten Hornemann, Giovanni D'Angelo, Vincenzo A. Gennarino
Summary: By studying individuals with de novo missense variants in CERT1, it was found that CERT autoregulation plays a central role in the control of sphingolipid biosynthetic flux. Inhibiting CERT pharmacologically can correct the morphological and motor abnormalities in CerTra syndrome, suggesting a potential therapeutic approach for patients.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Spectroscopy
Andreia Bento-Oliveira, Maria -Luisa C. J. Moita, Rodrigo F. M. de Almeida, Rados law Starosta
Summary: The p-methoxyphenylpiperazine motif is commonly found in biologically active molecules and can be used in various studies due to its weak fluorescence. This study conducted a comprehensive analysis of the absorption, excitation, and emission spectra of p-methoxyphenylpiperazine derivatives and determined the underlying mechanisms using computational methods. The study also explained the solvent effects observed in the electronic spectra of these compounds.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2024)
Article
Clinical Neurology
Safoora B. Syeda, Museer A. Lone, Payam Mohassel, Sandra Donkervoort, Pinki Munot, Marcondes C. Franca, Juan Eli Galarza-Brito, Matthias Eckenweiler, Alexander Asamoah, Kenneth Gable, Anirban Majumdar, Anke Schumann, Sita D. Gupta, Arpita Lakhotia, Perry B. Shieh, A. Reghan Foley, Kelly E. Jackson, Katherine R. Chao, Thomas L. Winder, Francesco Catapano, Lucy Feng, Janbernd Kirschner, Francesco Muntoni, Teresa M. Dunn, Thorsten Hornemann, Carsten G. Bonnemann
Summary: This study reports six patients from six independent families with juvenile amyotrophic lateral sclerosis (ALS) caused by a specific variant in the SPTLC2 gene. The findings confirm the importance of sphingolipid metabolism alterations in the pathogenesis of motor neuron diseases and suggest that avoiding serine supplementation may be a therapeutic strategy for SPT-associated ALS.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Clinical Neurology
Maike F. Dohrn, Danique Beijer, Museer A. Lone, Elif Bayraktar, Piraye Oflazer, Rotem Orbach, Sandra Donkervoort, A. Reghan Foley, Aubrey Rose, Michael Lyons, Raymond J. Louie, Kenneth Gable, Teresa Dunn, Sitong Chen, Matt C. Danzi, Matthis Synofzik, Carsten G. Boennemann, A. Nazli Basak, Thorsten Hornemann, Stephan Zuchner
Summary: This study identified gain-of-function mutations in SPTLC2 in juvenile ALS patients, leading to dysregulated sphingolipid synthesis and a key role in the pathogenesis of Mendelian periodic paralysis. This finding may open new therapeutic avenues for motor neuron diseases.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Medicine, Research & Experimental
Museer A. Lone, Mari J. Aaltonen, Aliza Zidell, Helio F. Pedro, Jonas A. Morales Saute, Shalett Mathew, Payam Mohassel, Carsten G. Bonnemann, Eric A. Shoubridge, Thorsten Hornemann
Summary: This study discovered different variants in the SPTLC1 gene that lead to distinct clinical presentations in Amyotrophic lateral sclerosis (ALS). The mutations impair the binding of ORMDL to the holoenzyme complex, resulting in changes in sphingolipid synthesis and lipid characteristics. Additionally, the mutations cause peripheral hereditary sensory and autonomic neuropathy type 1 (HSAN1).
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Review
Biochemistry & Molecular Biology
Xin Zhang, Tian Yuan, Xuhui Chen, Xuebo Liu, Jun Hu, Zhigang Liu
Summary: The prevalence of Alzheimer's disease is increasing due to aging population, and ApoE4 allele is identified as the primary genetic risk factor. However, emerging research suggests that dietary factors, such as DHA, can modify the risk of AD. The interplay between DHA and ApoE genotype within the brain needs further investigation. Early DHA supplementation may benefit cognitively normal older adults carrying the ApoE4 gene, while its effectiveness for AD patients is limited.
PROGRESS IN LIPID RESEARCH
(2024)
Review
Biochemistry & Molecular Biology
Chen Wu, Haiqin Chen, Yongchao Mei, Bo Yang, Jianxin Zhao, Catherine Stanton, Wei Chen
Summary: This review summarizes the recent advances in microbial conjugated linoleic acid (CLA) production, including the mechanisms of linoleic acid conversion to CLA, factors influencing CLA production and isomer composition, and strategies for enhancing CLA content and nutritional value in fermented products using microorganisms. The review aims to serve as a reference for microbial CLA production and expand the understanding of the potential probiotic role of microbial CLA producers.
PROGRESS IN LIPID RESEARCH
(2024)
