Article
Biochemistry & Molecular Biology
Steve Pedrini, James D. Doecke, Eugene Hone, Penghao Wang, Rohith Thota, Ashley Bush, Christopher C. Rowe, Vincent Dore, Victor L. Villemagne, David Ames, Stephanie Rainey-Smith, Giuseppe Verdile, Hamid R. Sohrabi, Manfred R. Raida, Kevin Taddei, Sam Gandy, Colin L. Masters, Pratishtha Chatterjee, Ralph N. Martins
Summary: The composition and functionality of HDL are altered in Alzheimer's Disease patients, which may impact regional brain volumetric data.
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Gaelle Rached, Youakim Saliba, Dina Maddah, Joelle Hajal, Viviane Smayra, Jules-Joel Bakhos, Klaus Groschner, Lutz Birnbaumer, Nassim Fares
Summary: This study investigates the role of TRPC3, a non-selective cation channel, in the regulation of insulin secretion and glucose control. The results show that TRPC3 is involved in glucose-stimulated insulin secretion and is functionally expressed in human and mouse islet beta cells. Activation of TRPC3 enhances insulin secretion and improves diabetes symptoms in animal models.
Article
Biochemistry & Molecular Biology
Marica Cariello, Roberto Salvia, Jennifer Hardfeldt, Marilidia Piglionica, David Rutigliano, Pasquale Caldarola, Alice Ossoli, Michele Vacca, Giusi Graziano, Stefano Battaglia, Roberta Zerlotin, Maria Arconzo, Lucilla Crudele, Carlo Sabba, Laura Calabresi, Antonio Moschetta
Summary: The study observed differences in cholesterol acceptability and efflux capacity in serum and monocytes of NSTEMI patients, indicating potential mechanisms for post-infarction treatment. The activation of LXR-driven cholesterol efflux capacity in intracoronary monocytes post-infarction may help overcome reduced serum cholesterol acceptance and inhibit local inflammation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Review
Biochemistry & Molecular Biology
Leonie Schoch, Lina Badimon, Gemma Vilahur
Summary: Increasing doubt has been raised over the HDL-cholesterol hypothesis, with evidence pointing towards the complexity and molecular changes in HDL particles. Chemical modifications, compositional changes, and miRNA cargo have been identified as factors contributing to the ineffectiveness of HDL particles. Overcoming challenges is crucial to bringing hope to HDL-targeted approaches.
Article
Physiology
Shichen Huang, Zhiyuan Li, Yuhan Sun, Baiyi Chen, Yuxin Jiang, Feng Hong
Summary: CD34 could serve as a biomarker for islet beta-cells, with its expression and number being inversely correlated with islet alpha-cells. This suggests the potential of CD34 as a diagnostic biomarker for early diabetes.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Johanna F. Schachtl-Riess, Stefan Coassin, Claudia Lamina, Egon Demetz, Gertraud Streiter, Richard Hilbe, Florian Kronenberg
Summary: The study found that the per-well method for measuring CEC had lower rejection rates and coefficients of variation compared to the time zero method, and the use of four controls on each plate improved assay performance for both methods. Additionally, the choice of lysis reagents, cell numbers, and assay setup significantly impact the quality and reliability of CEC quantification.
JOURNAL OF LIPID RESEARCH
(2021)
Article
Endocrinology & Metabolism
Genki Kobayashi, Hiroshi Okada, Masahide Hamaguchi, Kazushiro Kurogi, Hiroaki Murata, Masato Ito, Michiaki Fukui
Summary: This study investigated the association between LDL cholesterol, HDL cholesterol, and LDL/HDL ratio and the incidence of diabetes, and identified the cut-off values for incident diabetes.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Natsuki Eguchi, Kimia Damyar, Michael Alexander, Donald Dafoe, Jonathan R. T. Lakey, Hirohito Ichii
Summary: Islet cell transplantation is a favorable therapeutic approach for Type 1 Diabetes, but there are limitations in the process, including oxidative stress that leads to the loss of islet cells. Therefore, exploring the application of antioxidants in transplantation is crucial.
Article
Biology
Jialiang Yang, Yuhong Chen, Tongdan Zou, Bai Xue, Fang Yang, Xiangzhou Wang, Yibo Huo, Boyun Yan, Yuxia Xu, Shiyu He, Yi Yin, Jing Wang, Xiong Zhu, Lin Zhang, Yu Zhou, Zhengfu Tai, Ping Shuai, Man Yu, Qian Luo, Yilian Cheng, Bo Gong, Xianjun Zhu, Jing Zhang, Xinghuai Sun, Ying Lin, Houbin Zhang, Zhenglin Yang
Summary: This study reveals that lower ABCA1 expression and lower HDL are risk factors for primary open-angle glaucoma (POAG). Ablation of Abca1 in mice leads to elevated cholesterol levels in the retina, causing a POAG-like phenotype. Treatment with atorvastatin reduces cholesterol levels in the retina, improving metabolism and protecting retinal ganglion cells.
SCIENCE CHINA-LIFE SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Yasuhiro Endo, Masanori Fujita, Katsunori Ikewaki
Summary: Cardiovascular disease (CVD) is the leading cause of death in Western countries. Recent epidemiology studies have shown a U-shaped relationship between high-density lipoprotein cholesterol (HDL-C) levels and CVD mortality, with increased mortality in patients with extremely high HDL-C levels. HDL-C raising therapy using nicotinic acids or CETP inhibitors has shown limited efficacy in reducing CVD events. As a result, the focus has shifted to evaluating HDL functionality as a novel biomarker for CVD risk. This review provides an overview of the current status and future perspectives on HDL functions, based on findings from basic research and clinical trials.
Article
Biochemistry & Molecular Biology
Yume Mutsuda, Tsunehiro Miyakoshi, Yuna Horiuchi, Takahiro Kameda, Minoru Tozuka, Ryunosuke Ohkawa
Summary: During the past decade, the evaluation of HDL functionality has been extensively studied to predict cardiovascular disease risk. However, the use of cholesterol efflux capacity as a biomarker has faced technical challenges. A new method, using immobilized liposome-bound magnetic beads (ILMs), was developed as a replacement for the conventional method. The ILM method showed good performance and correlation with the previous method when evaluating the cholesterol efflux capacity of serum samples from healthy subjects.
BIOSCIENCE REPORTS
(2023)
Article
Endocrinology & Metabolism
Adrian Post, Erwin Garcia, Eke G. Gruppen, Daan Kremer, Margery A. Connelly, Stephan J. L. Bakker, Robin P. F. Dullaart
Summary: In euthyroid individuals, higher levels of FT3 are associated with higher total HDL particle concentration and lower HDL particle size. The associations with FT4 or TSH are less pronounced or not significant.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Nutrition & Dietetics
Pedro G. S. Braga, Fatima R. Freitas, Andre L. L. Bachi, Gislene R. Amirato, Roberta V. Baroni, Maria Janieire N. N. Alves, Rodolfo P. Vieira, Mauro W. Vaisberg, Marlene N. Aldin, Roberto Kalil Filho, Antonio M. Figueiredo Neto, Nagila R. T. Damasceno, Thauany M. Tavoni, Raul C. Maranhao, Zhen Chen
Summary: This study investigated the effects of regular physical activity on two important functions of HDL, namely cholesterol reception and antioxidant capacity. The results showed that active individuals had higher HDL-C levels, better cholesterol transfer, and more HDL subfractions compared to inactive individuals. Age did not have a significant effect on these functions.
Review
Biochemistry & Molecular Biology
Carla Borras, Aina Mercer, Sonia Sirisi, Daniel Alcolea, Joan Carles Escola-Gil, Francisco Blanco-Vaca, Mireia Tondo
Summary: This work aims to review the mechanisms of high-density lipoprotein (HDL)-mediated cholesterol trafficking in the central nervous system (CNS) in the context of Alzheimer's disease (AD). It explores the relationship between HDL-mediated cholesterol transport and Aβ peptide accumulation and apolipoprotein E (ApoE)-mediated cholesterol transport. The existing data suggest decreased cholesterol efflux and impaired cholesterol entry into neurons among patients with AD. However, most studies in this field have been performed in cells that are not physiologically relevant for CNS pathology, which is a major flaw. Further investigations are needed to clarify the role of cholesterol trafficking in AD pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Manuela Casula, Ornella Colpani, Sining Xie, Alberico L. Catapano, Andrea Baragetti
Summary: Recent studies on the role of high-density lipoprotein cholesterol (HDL-C) in cardiovascular disease have found a complex U-shaped relationship between HDL levels and cardiovascular mortality risk. Additionally, genetic studies, Mendelian randomization approaches, and clinical trials have challenged the traditional notion of a causal link between HDL-C levels and cardiovascular protection.
Article
Biochemistry & Molecular Biology
Ligia Fao, Patricia Coelho, Luis Duarte, Rita Vilaca, Michael R. Hayden, Sandra I. Mota, Ana Cristina Rego
Summary: This study demonstrates that c-Src/Fyn proteins play an important role in controlling mitochondrial function and redox regulation in Huntington's disease (HD). Restoring c-Src/Fyn levels in HD improves mitochondrial morphology and function, reducing the levels of oxidant species and cell death. These findings suggest that c-Src/Fyn could be a potential therapeutic target for HD.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Article
Cell Biology
Shao-Ming Wang, Hsiang-En Wu, Yuko Yasui, Michal Geva, Michael Hayden, Tangui Maurice, Mauro Cozzolino, Tsung-Ping Su
Summary: Autophagy is a crucial cellular process with implications in various diseases. In this study, researchers discovered that the molecular chaperone SIGMAR1 is involved in the transport of TFEB into the nucleus by chaperoning the NP protein POM121, which is responsible for recruiting KPNB1. The disruption of this process in ALS-FTD patients with the C9orf72 subtype leads to impaired autophagy. However, overexpression of SIGMAR1 or POM121, as well as treatment with pridopidine, a SIGMAR1 agonist, can rescue these deficits, suggesting their potential therapeutic use.
Article
Multidisciplinary Sciences
Vera J. M. Nies, Dicky Struik, Sihao Liu, Weilin Liu, Janine K. Kruit, Michael Downes, Tim van Zutphen, Henkjan J. Verkade, Ronald M. Evans, Johan W. Jonker
Summary: This study found that FGF1 can increase glucose uptake in adipocytes by activating GLUT4 protein. Furthermore, prolonged exposure to FGF1 can stimulate adipocyte glucose uptake by transcription of GLUT1 protein.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Pawel Joachimiak, Adam Ciesiolka, Emilia Kozlowska, Pawel M. Switonski, Grzegorz Figura, Agata Ciolak, Grazyna Adamek, Magdalena Surdyka, Zaneta Kalinowska-Poska, Maciej Figiel, Nicholas S. S. Caron, Michael R. R. Hayden, Agnieszka Fiszer
Summary: This study used SNP variants to quantitatively determine the allele-specific expression levels in patient-derived cell lines for spinocerebellar ataxia type 3 (SCA3) and Huntington's disease (HD). They found differences in allele expression levels and developed a reliable and quantitative method using SNP-based droplet digital PCR (ddPCR) to analyze low abundant transcripts. This allele-selective approach provides insights into allele-related mechanisms and can improve understanding of polyglutamine diseases.
Article
Physiology
Fanny L. Lemarie, Shaun S. Sanders, Yen Nguyen, Dale D. O. Martin, Michael R. Hayden
Summary: Huntington's disease is a neurodegenerative disorder caused by CAG repeat expansion in the HTT gene. We found that huntingtin protein can be palmitoylated at cysteine 214, and proteolytic cleavage at aspartate 552 leads to myristoylation at glycine 553. Blocking caspase cleavage at aspartate 586 increases myristoylation of huntingtin and promotes the interaction between C-terminal and N-terminal fragments.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Neurosciences
James P. Mackay, Amy I. Smith-Dijak, Ellen T. Koch, Peng Zhang, Evan Fung, Wissam B. Nassrallah, Caodu Buren, Mandi Schmidt, Michael R. Hayden, Lynn A. Raymond
Summary: Miniature neurotransmission is increased in the Huntington disease (HD) model, associated with abnormal endoplasmic reticulum (ER) calcium handling. These abnormalities influence neurotransmission indirectly, without direct ER calcium release into the cytoplasm. However, in cortical cultures and brain slices, there are no significant differences in calcium release between the HD-model neurons and wild-type cells.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Neurosciences
Angela J. C. Tol, Kaja Hribar, Janine Kruit, Laura Bongiovanni, Marcel A. Vieira-Lara, Mirjam H. Koster, Niels J. Kloosterhuis, Rick Havinga, Martijn Koehorst, Alain de Bruin, Barbara M. Bakker, Maaike H. Oosterveer, Eline M. van der Beek
Summary: Hyperglycaemia in pregnancy (HIP) is a pregnancy complication characterized by mild to moderate hyperglycaemia that negatively impacts the health of mother and child. The study investigated the impact of gestational diabetes mellitus (GDM) and pre-gestational diabetes mellitus (PDM) on maternal health and pregnancy outcomes. The findings indicate that GDM and PDM increase the risk of postpartum non-alcoholic fatty liver disease (NAFLD) development, highlighting the need for earlier monitoring of maternal glycaemia and more rigorous follow-up of maternal health after GDM and PDM pregnancy in humans.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Pharmacology & Pharmacy
Andrea C. Postmus, Janine K. Kruit, Roos E. Eilers, Rick Havinga, Mirjam H. Koster, Yoshikazu Johmura, Makoto Nakanishi, Bart van de Sluis, Johan W. Jonker
Summary: Cancer survivors who undergo chemotherapy, such as DOX, have an increased risk of developing chronic metabolic diseases. However, in a mouse study, drug-induced cellular senescence did not have a significant impact on long-term metabolic effects.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2023)
Article
Clinical Neurology
Borje Darpo, Michal Geva, Georg Ferber, Yigal Paul Goldberg, Andres Cruz-Herranz, Munish Mehra, Richard Kovacs, Michael R. Hayden
Summary: Pridopidine, a selective sigma-1 receptor agonist, shows a favorable cardiac safety profile at the therapeutic dose of 45 mg bid, with no clinically relevant effect on the QT interval.
NEUROLOGY AND THERAPY
(2023)
Article
Biotechnology & Applied Microbiology
Neel Mehta, Renald Gilbert, Parminder S. Chahal, Maria J. Moreno, Nasha Nassoury, Nathalie Coulombe, Viktoria Lytvyn, Mario Mercier, Dorothy Fatehi, Wendy Lin, Emily M. Harvey, Lin-Hua Zhang, Nazila Nazemi-Moghaddam, Seyyed Mehdy Elahi, Colin J. D. Ross, Danica B. Stanimirovic, Michael R. Hayden
Summary: This study aimed to develop a more efficacious AAV gene therapy vector for the treatment of LPLD. The researchers identified AAV8 pVR59 as a superior vector compared to AAV1 (Glybera), with significantly better therapeutic effects at lower doses. AAV8 pVR59 treatment led to long-term correction of LPLD and improvement in pathology.
HUMAN GENE THERAPY
(2023)
Article
Biotechnology & Applied Microbiology
Fabio Duarte, Gabriel Vachey, Nicholas S. Caron, Melanie Sipion, Maria Rey, Anselme L. Perrier, Michael R. Hayden, Nicole Deglon
Summary: Huntington's disease is a fatal neurodegenerative disorder that can be treated by inactivating the mutated HTT gene. One approach to selectively inactivate the mutant allele is by using the CRISPR/Cas9 system to remove the first exon of the mutated HTT. However, the frequency of deletion events is still uncertain.
HUMAN GENE THERAPY
(2023)
Meeting Abstract
Oncology
J. C. Hall, T. H. Ung, T. L. McCleary, C. F. Chuang, I. C. Gibbs, S. G. Soltys, M. Hayden, G. Li, E. Pollom, S. D. Chang, A. Meola
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2022)
Meeting Abstract
Clinical Neurology
Nicholas S. Caron, Arsalan S. Haqqani, Akshdeep Sandhu, Amirah E. Aly, Hailey Findlay Black, Jeffrey N. Bone, Jodi L. McBride, Abedelnasser Abulrob, Danica Stanimirovic, Blair R. Leavitt, Michael R. Hayden
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Clinical Neurology
Michal Geva, Shao-Ming Wang, Hsiang-En Wu, Lior Ankol, Ariel Ionescu, Tal Gradus-Pery, Noga Gershoni-Emek, Y. Paul Goldberg, Tsung-Ping Su, Eran Perlson, Michael R. Hayden
Article
Clinical Neurology
Nicholas S. Caron, Arsalan S. Haqqani, Akshdeep Sandhu, Amirah E. Aly, Hailey Findlay Black, Jeffrey N. Bone, Jodi L. McBride, Abedelnasser Abulrob, Danica Stanimirovic, Blair R. Leavitt, Michael R. Hayden
Summary: The study aims to identify molecular biomarkers in the cerebrospinal fluid (CSF) to improve predictions and understanding of Huntington disease. The researchers investigated protein candidates in CSF from individuals with Huntington disease and healthy controls, and found both known and novel biomarkers associated with the disease. They found that combinations of CSF proteins can better stratify individuals based on disease status and severity, and may be useful in predicting disease onset and assessing therapeutic response in clinical trials.
BRAIN COMMUNICATIONS
(2022)
