Article
Cell Biology
Tamara L. Paget, Emma J. Parkinson-Lawrence, Paul J. Trim, Chiara Autilio, Madhuriben H. Panchal, Grielof Koster, Mercedes Echaide, Marten F. Snel, Anthony D. Postle, Janna L. Morrison, Jesus Perez-Gil, Sandra Orgeig
Summary: In MPS IIIA patients, alterations in biochemical and biophysical properties of alveolar surfactant in lung tissue and BALF indicate potential impairment in lung function.
Article
Cell Biology
Tayler F. L. Wishart, Frank J. Lovicu
Summary: Heparan sulphate proteoglycans (HSPGs) are composed of a core protein and sulphated HS-glycosaminoglycan (GAG) chains. These HS-GAG chains bind to and regulate the activity of HS-binding proteins, including growth factors, playing a crucial role in cellular processes during lens development. The different localisation of HSPG core proteins suggests their specialized roles in lens induction and morphogenesis.
Review
Biochemistry & Molecular Biology
Anthony J. Hayes, James Melrose
Summary: The recent discovery of nuclear and perinuclear perlecan in annulus fibrosus and nucleus pulposus cells and its potential roles in stabilizing the nucleus through interactions with nuclear envelope components raises the possibility of regulating gene expression. The presence of perlecan in tumor cell nuclei suggests its involvement in disease progression, while this review aims to explore its roles in both normal and malignant cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Xuefang Pan, Mahsa Taherzadeh, Poulomee Bose, Rachel Heon-Roberts, Annie L. A. Nguyen, TianMeng Xu, Camila Para, Yojiro Yamanaka, David A. Priestman, Frances M. Platt, Shaukat Khan, Nidhi Fnu, Shunji Tomatsu, Carlos R. Morales, Alexey Pshezhetsky
Summary: The majority of MPS IIIC patients have missense variants causing misfolding of HGSNAT, which can be potentially treated with pharmacological chaperones. A novel mouse model expressing a misfolded HGSNAT variant shows deficits in memory and neuroimmune response, which can be rescued by treatment with a chaperone, glucosamine.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Patryk Lipinski, Krzysztof Szczaluba, Piotr Buda, Ekaterina Y. Zakharova, Galina Baydakova, Agnieszka Lugowska, Agnieszka Rozdzynska-Swiatkowska, Zuzanna Cyske, Grzegorz Wegrzyn, Agnieszka Pollak, Rafal Ploski, Anna Tylki-Szymanska
Summary: This article reports a Polish MPS-PS patient with a novel VPS33A gene variant and new clinical features. Functional analysis revealed some related biomarkers, and comparison with other cases helped broaden understanding of the disease phenotype.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
Yingjun Liang, Xiaolan Gao, Deyun Lu, Huiwen Zhang, Zhang
Summary: This study analyzed the clinical, biochemical, and genetic characteristics of ten Chinese MPS IIIC patients from eight families. The mean age at symptom onset was 4.2 years old, and the mean age at diagnosis was 7.6 years old, suggesting a delay in diagnosis. The most common presenting symptoms were speech deterioration, followed by mental deterioration, hyperactivity, and hepatomegaly. All mutant alleles of the patients were identified, including eleven different HGSNAT variants, with the most common one being a previously reported variant.
METABOLIC BRAIN DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Jenna Magat, Samantha Jones, Brian Baridon, Vishal Agrawal, Hio Wong, Alexander Giaramita, Linley Mangini, Britta Handyside, Catherine Vitelli, Monica Parker, Natasha Yeung, Yu Zhou, Erno Pungor, Ilya Slabodkin, Olivia Gorostiza, Allora Aguilera, Melanie J. Lo, Saida Alcozie, Terri M. Christianson, Pascale M. N. Tiger, Jon Vincelette, Sylvia Fong, Geuncheol Gil, Chuck Hague, Roger Lawrence, Daniel J. Wendt, Jonathan H. Lebowitz, Stuart Bunting, Sherry Bullens, Brett E. Crawford, Sushmita M. Roy, Josh C. Woloszynek
Summary: This study demonstrates the efficacy of rhSGSH in treating MPS IIIA through intracerebroventricular delivery. RhSGSH can completely normalize lysosomal HS storage and markers of neuroimmune response.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Respiratory System
Eleni Papakonstantinou, Maria-Elpida Christopoulou, Meropi Karakioulaki, Leticia Grize, Michael Tamm, Daiana Stolz
Summary: The study aimed to investigate the association between plasma levels of heparan sulphate (HS) and the aetiology of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The results showed that HS levels were higher in COPD patients compared to non-COPD controls, and significantly increased during AECOPD. The increase of HS levels was associated with the aetiology of exacerbations, especially in cases with bacterial and viral coinfections.
Article
Genetics & Heredity
Francesca Maccari, Laura Rigon, Veronica Mantovani, Fabio Galeotti, Marika Salvalaio, Francesca D'Avanzo, Alessandra Zanetti, Federica Capitani, Orazio Gabrielli, Rosella Tomanin, Nicola Volpi
Summary: This study examined the changes in plasma and urinary GAGs in Ids knock-out (Ids-ko) mice over a 24-week follow-up, with and without enzyme replacement therapy (ERT). Untreated Ids-ko mice showed increased levels of GAGs, while ERT was associated with a decrease in heparan-sulfate (HS) and partially in chondroitin-sulfate (CS) and dermatan-sulfate (DS). Various structural parameters were altered in untreated mice and partially restored after ERT, although not reaching physiological levels.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Article
Genetics & Heredity
Erin T. Strovel, Kristina Cusmano-Ozog, Tim Wood, Chunli Yu
Summary: Assays that measure lysosomal enzyme activity are crucial for diagnosing and screening lysosomal storage disorders. This document provides guidance for clinical enzyme testing, including test performance variables and the need for follow-up molecular testing.
GENETICS IN MEDICINE
(2022)
Review
Endocrinology & Metabolism
Berna Seker Yilmaz, James Davison, Simon A. Jones, Julien Baruteau
Summary: MPS III, a neurodegenerative disease, currently lacks disease-modifying therapy, but multiple curative therapies have been developed, emphasizing the importance of early treatment before extensive neuronal loss occurs.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Marissa L. Maciej-Hulme, Eamon Dubaissi, Chun Shao, Joseph Zaia, Enrique Amaya, Sabine L. Flitsch, Catherine L. R. Merry
Summary: The study presents a simple method for selective inhibition of HS biosynthesis using a small molecule compound Ac(4)GalNAz. This inhibition is transient and dose-dependent, successfully reducing HS expression without affecting CS production. The utility of this method is demonstrated in both cell culture and whole organisms, proving its potential as a tool for HS inhibition in biological systems.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Applied
Noemi Veraldi, Isabelle Dentand Quadri, Yohan van de Looij, Laura Malaguti Modernell, Corinne Sinquin, Agata Zykwinska, Benjamin B. Tournier, Fabien Dalonneau, Honglian Li, Jin-Ping Li, Philippe Millet, Romain Vives, Sylvia Colliec-Jouault, Ariane de Agostini, Eduardo Farias Sanches, Stephane V. Sizonenko
Summary: Derivative A5_3, derived from marine polysaccharides, inhibits intracellular HS accumulation and shows protective effects on brain metabolism and microstructure in MPSIIIA mice.
CARBOHYDRATE POLYMERS
(2023)
Article
Medicine, Research & Experimental
Kalliopi Sofou, Kolja Meier, Leslie E. Sanderson, Debora Kaminski, Laia Montoliu-Gaya, Emma Samuelsson, Maria Blomqvist, Lotta Agholme, Jutta Gaertner, Chris Muehlhausen, Niklas Darin, Tahsin Stefan Barakat, Lars Schlotawa, Tjakko van Ham, Jorge Asin Cayuela, Fredrik H. Sterky
Summary: Patients with lysosomal storage disease-like symptoms were found to have homozygous mutations in VPS16, resulting in impaired cellular functions such as transferrin uptake and lysosomal accumulation, which were rescued by re-expression of VPS16. Disrupted vps16 expression in zebrafish led to developmental defects and similar lysosomal and autophagosomal accumulation in the brain. This expands the understanding of diseases resulting from mutations in HOPS/CORVET subunits.
EMBO MOLECULAR MEDICINE
(2021)
Article
Cell Biology
Ana A. Jones, Elvira Diamantopoulou, Sarah Baxendale, Tanya T. Whitfield
Summary: Epithelial morphogenesis of the zebrafish inner ear depends on the production and localization of glycosaminoglycans, particularly hyaluronan and proteoglycans, which play critical roles in epithelial projection outgrowth and otolith development.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jianling Xie, Kaikai Shen, Ashley T. Jones, Jian Yang, Andrew R. Tee, Ming Hong Shen, Mengyuan Yu, Swati Irani, Derick Wong, James E. Merrett, Roman Lenchine, Stuart De Poi, Kirk B. Jensen, Paul J. Trim, Marten F. Snel, Makoto Kamei, Sally Kim Martin, Stephen Fitter, Shuye Tian, Xuemin Wang, Lisa M. Butler, Andrew C. W. Zannettino, Christopher G. Proud
Summary: This study uncovers a novel feedback loop in which mTORC1 represses MNK2 activity and oncogenic signaling through eIF4E phosphorylation, providing insights into the reciprocal regulation of these two oncogenic pathways.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Endocrinology & Metabolism
Meghan L. Douglass, Helen Beard, Andrew Shoubridge, Nazzmer Nazri, Barbara King, Paul J. Trim, Stephen K. Duplock, Marten F. Snel, John J. Hopwood, Kim M. Hemsley
Summary: Lysosomal dysfunction may play a role in neurodegenerative disorders like Parkinson's disease. Mutations in genes encoding lysosomal enzymes have been associated with PD, and studies on mice with a Sgsh gene mutation revealed impaired behavior and brain structure, but no overt disease lesions associated with PD or other neurodegenerative disorders were observed.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Biochemical Research Methods
Jacob X. M. Truong, Xander Spotbeen, Jake White, Johannes V. Swinnen, Lisa M. Butler, Marten F. Snel, Paul J. Trim
Summary: MALDI-MSI is a molecular imaging technique used to study the abundance and distribution of lipids in tissues. Challenges in sample pre-treatment and preparation have hindered the analysis of clinical tissues. A new method has been developed to remove O.C.T. and endogenous salts simultaneously, preventing analyte suppression, simplifying data interpretation, and improving sensitivity.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Miranda P. Ween, Jake B. White, Hai B. Tran, Violet Mukaro, Charles Jones, Matthew Macowan, Gregory Hodge, Paul J. Trim, Marten F. Snel, Sandra J. Hodge
Summary: The study revealed that in COPD patients, CD1b expression is upregulated in the airways, levels of oxidized lipids are increased, and malondialdehyde levels are significantly elevated. Oxidized lipids can enhance CD1b expression in macrophages, cause toxicity in bronchial epithelial cells, and reduce phagocytic capacity in macrophages.
SCIENTIFIC REPORTS
(2021)
Article
Veterinary Sciences
R. D. Jolly, K. E. Dittmer, B. R. Jones, A. J. Worth, K. G. Thompson, A. C. Johnstone, D. N. Palmer, N. S. Van de Water, K. M. Hemsley, D. J. Garrick, B. G. Winchester, S. U. Walkley
Summary: In the past 50 years, there have been significant advances in knowledge and technology regarding genetic diseases, enabling more cost-effective ways to control these diseases. Research on genetic diseases of animals at Massey University has made a significant contribution to veterinary medicine, provided new biological knowledge, and advanced our understanding of similar disorders in human patients.
NEW ZEALAND VETERINARY JOURNAL
(2021)
Article
Cell Biology
Tamara L. Paget, Emma J. Parkinson-Lawrence, Paul J. Trim, Chiara Autilio, Madhuriben H. Panchal, Grielof Koster, Mercedes Echaide, Marten F. Snel, Anthony D. Postle, Janna L. Morrison, Jesus Perez-Gil, Sandra Orgeig
Summary: In MPS IIIA patients, alterations in biochemical and biophysical properties of alveolar surfactant in lung tissue and BALF indicate potential impairment in lung function.
Article
Oncology
Lisa M. Butler, Chui Yan Mah, Jelle Machiels, Andrew D. Vincent, Swati Irani, Shadrack M. Mutuku, Xander Spotbeen, Muralidhararao Bagadi, David Waltregny, Max Moldovan, Jonas Dehairs, Frank Vanderhoydonc, Katarzyna Bloch, Rajdeep Das, Jurgen Stahl, James G. Kench, Thomas Gevaert, Rita Derua, Etienne Waelkens, Zeyad D. Nassar, Luke A. Selth, Paul J. Trim, Marten F. Snel, David J. Lynn, Wayne D. Tilley, Lisa G. Horvath, Margaret M. Centenera, Johannes Swinnen
Summary: The study identified distinct lipid features in prostate cancer tissues, including enhanced fatty acid synthesis and elongation. Targeting the regulation of lipid composition may be a crucial therapeutic approach for prostate cancer.
Article
Microbiology
Felise G. Adams, Claudia Trappetti, Jack K. Waters, Maoge Zang, Erin B. Brazel, James C. Paton, Marten F. Snel, Bart A. Eijkelkamp
Summary: The study found that Acinetobacter baumannii may rely on different sources of fatty acids during infection and synthesize fatty acids in different environments. Additionally, it is the first to reveal the importance of balancing de novo synthesis and acquisition of fatty acids in a Gram-negative bacterium during infection.
Article
Chemistry, Analytical
Jake B. White, Paul J. Trim, Thalia Salagaras, Aaron Long, Peter J. Psaltis, Johan W. Verjans, Marten F. Snel
Summary: Chromatography is commonly used to simplify samples before mass spectrometry analysis, and the use of retention time (RT) for lipid identification is gaining popularity. This study demonstrates a strong correlation in chromatographic separation of lipids with different headgroups but the same fatty acid motive. The correlation is used for interclass RT conversion (IC-RTC), allowing the prediction of RT of one lipid subclass based on another. A glycerophospholipid RT library is built using ECN modeling and IC-RTC, and successfully applied to identify lipid species in a patient cohort undergoing surgery.
ANALYTICAL CHEMISTRY
(2022)
Review
Oncology
Shadrack M. Mutuku, Xander Spotbeen, Paul J. Trim, Marten F. Snel, Lisa M. Butler, Johannes Swinnen
Summary: Prostate cancer is a heterogeneous disease and treatment decisions are challenging. In this article, the emerging importance of rewired lipid metabolism as a source for biomarkers and therapeutic targets for prostate cancer is highlighted. The spatial mapping of lipids and related metabolic pathways and its potential for future implementation in treatment decision-making are evaluated. The detection and management of prostate cancer have improved, but distinguishing between indolent and aggressive forms of the disease remains a challenge. Spatial analytical approaches, such as mass spectrometry-based lipid imaging and gene-based spatial omics technologies, are discussed as potential solutions. The study aims to evaluate the future implementation of spatial lipidomics and transcriptomics for prognostication, target identification, and treatment decision-making for prostate cancer.
Article
Veterinary Sciences
R. D. Jolly, M. R. Perrott, M. R. Alley, S. A. Hunter, A. Pas, H. Beard, K. M. Hemsley, G. Greaves
Summary: This study investigated the pathogenesis of a disease in takahe (Porphyrio hochstetteri) characterized by intracytoplasmic inclusion bodies in lower motor neurons. Four takahe birds from different wildlife sanctuaries in New Zealand were examined, and two types of inclusion bodies were found in the motor neurons of the spinal cord and brain stem. The larger globoid bodies were found to be endoplasmic reticulum storage disease, while the smaller granular bodies showed misfolded protein entering the lysosomal system via endoplasmic reticulum autophagy. The cause of the disease is likely genetic or predisposed, and has clinical relevance.
NEW ZEALAND VETERINARY JOURNAL
(2023)
Review
Biochemistry & Molecular Biology
Leanne K. Winner, Mary-Louise Rogers, Marten F. Snel, Kim M. Hemsley
Summary: Sanfilippo syndrome is an autosomal recessive inherited disorder that causes dementia in children. Early symptoms include delayed language development, hyperactivity, and insomnia, followed by the loss of acquired skills. There are no approved treatments, and the disease usually leads to death by age 18. Newborn screening for Sanfilippo syndrome would allow for early diagnosis and treatment, but there is a need for tools and biomarkers to provide pre-symptomatic prognosis. This review discusses the development of biomarker assays for Sanfilippo syndrome based on known neuropathological pathways.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Neurosciences
Kim M. Hemsley, Helen Beard, Glyn Chidlow, Teresa Mammone, Leanne K. Winner, Daniel Neumann, Barbara King, Marten F. Snel, Paul J. Trim, Robert J. Casson
Summary: Optical coherence tomography (OCT) is a non-invasive method that can be used to rapidly and quantitatively examine the integrity of the neuroretina. It has been shown that OCT can be used to observe retinal thinning in patients with childhood dementia, and to assess the improvement of retinal structure after treatment. Furthermore, OCT can provide insights into other childhood dementias based on the correlation between retinal and brain degeneration in Sanfilippo syndrome.
EXPERIMENTAL NEUROLOGY
(2024)
Article
Biochemistry & Molecular Biology
Pei-Yang Gao, Ya-Nan Ou, Yi-Ming Huang, Zhi-Bo Wang, Yan Fu, Ya-Hui Ma, Qiong-Yao Li, Li-Yun Ma, Rui-Ping Cui, Yin-Chu Mi, Lan Tan, Jin-Tai Yu
Summary: Liver function may play a role in the progression of Alzheimer's disease. The study found that as AD progressed, certain liver function markers increased while others decreased. The relationship between liver function and CSF AD biomarkers indicates a potential mediation effect on cognition.
JOURNAL OF NEUROCHEMISTRY
(2024)