Review
Neurosciences
Chris W. J. van der Weijden, David Vallez Garcia, Ronald J. H. Borra, Patrick Thurner, Jan F. Meilof, Peter-Jan van Laar, Rudi A. J. O. Dierckx, Ingomar W. Gutmann, Erik F. J. de Vries
Summary: This systematic review examines the performance of MRI methods for myelin quantification, showing a fairly good correlation with histology and good reproducibility. However, due to limited validation data and variability in performance between studies, the optimal MRI method for myelin quantification has yet to be determined.
Article
Neurosciences
Vilma Alanko, Adhara Gaminde-Blasco, Tania Quintela-Lopez, Raul Loera-Valencia, Alina Solomon, Ingemar Bjorkhem, Angel Cedazo-Minguez, Silvia Maioli, Graziella Tabacaru, Maria Latorre-Leal, Carlos Matute, Miia Kivipelto, Elena Alberdi, Anna Sandebring-Matton
Summary: Oxidized cholesterol metabolite 27-hydroxycholesterol (27-OH) is a potential link between hypercholesterolemia and neurodegenerative diseases as it can cross the blood-brain barrier. This study found that high levels of 27-OH can impact oligodendrocyte function and contribute to the disconnection of neural networks in neurodegenerative diseases.
Article
Immunology
Saade Abdalkareem Jasim, Hamzah H. Kzar, Mohammed Haider Hamad, Irfan Ahmad, Moaed E. Al-Gazally, Shukhrat Ziyadullaev, R. Sivaraman, Mohammed Abed Jawad, Ali Thaeer Hammid, Khulood H. Oudaha, Sajad Karampoor, Rasoul Mirzaei
Summary: Oxysterols are cholesterol metabolites with various biological functions, including their involvement in cancer development and immunological suppression. Specifically, 27-hydroxycholesterol (27-HC) may act as an estrogen and promote the growth of estrogen receptor (ER) positive breast cancer cells. However, the precise role of 27-HC in cancer promotion and progression is still debatable, and more research is needed to uncover the exact function of these molecules.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Immunology
G. E. Denaroso, Z. Smith, C. G. Angeliu, V. T. Cheli, C. Wang, P. M. Paez
Summary: In this study, the role of astrocytic voltage-gated Ca++ channels in autoimmune inflammation and demyelination in the central nervous system (CNS) was investigated using the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis combined with Cav1.2 conditional knock-out mice. The results showed that deleting Cav1.2 channels in astrocytes significantly reduced the severity of the disease and protected the spinal cord from autoimmune demyelination.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Biochemistry & Molecular Biology
Laetitia Pouzol, Nadege Baumlin, Anna Sassi, Melanie Tunis, Julia Marrie, Enrico Vezzali, Herve Farine, Ulrich Mentzel, Marianne M. Martinic
Summary: Current strategies for treating demyelinating diseases like multiple sclerosis focus on anti-inflammatory or immunomodulatory drugs. The CXCR7 receptor antagonist ACT-1004-1239 shows promise in reducing disease severity, decreasing neuroinflammation, and promoting myelin repair in experimental models.
Article
Clinical Neurology
Sara Ribes Garcia, Jessica Castillo-Villalba, Raquel Gasque Rubio, Sara Carratala Bosca, Laura Cubas-Nunez, Carmen Alcala, Francisco Carlos Perez-Miralles, Casanova Estruch Bonaventura
Summary: This study aimed to analyze whether the presence of IgM oligoclonal bands against lipids is associated with disease progression in multiple sclerosis. The results showed that 81.9% of patients had IgM oligoclonal bands against lipids, but no association with other poor prognostic variables was found.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2023)
Article
Immunology
Philippe Horellou, Alienor de Chalus, Laetitia Giorgi, Carole Leroy, Pascale Chretien, Salima Hacein-Bey-Abina, Christine Bourgeois, Xavier Mariette, Che Serguera, Roger Le Grand, Kumaran Deiva
Summary: The study identified differences in MOG antigenic immunological response among MOGAD, MS, and control patients, as well as between relapsing and non-relapsing subgroups of MOGAD. CD4(+) Th2 and Th17 cells were found to be involved in the pathophysiology of MOGAD in children, while the opposite response of T-regs to rh-MOG in relapsing and non-relapsing MOGAD patients may explain relapses in this recurrent pediatric autoimmune disease.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Paola Giussani, Alessandro Prinetti, Cristina Tringali
Summary: Sphingolipids play a crucial role in brain development and myelin formation in the nervous system, with abnormalities potentially leading to demyelinating diseases like multiple sclerosis. Understanding the bioactive molecules associated with sphingolipid metabolism, such as ceramide and sphingosine, may help identify potential targets for therapies.
JOURNAL OF NEUROCHEMISTRY
(2021)
Review
Clinical Neurology
Lindsey B. De Lott, Jeffrey L. Bennett, Fiona Costello
Summary: Optic neuritis is an inflammatory optic neuropathy that is often associated with demyelinating disorders of the central nervous system. However, it is frequently misdiagnosed in clinical practice, leading to inappropriate treatment or delays in diagnosis. With an increased understanding of immunopathology, novel disease management strategies are emerging to minimize vision loss and improve long-term surveillance.
JOURNAL OF NEUROLOGY
(2022)
Article
Immunology
Jose Fernandez-Velasco, Enric Monreal, Jens Kuhle, Virginia Meca-Lallana, Jose Meca-Lallana, Guillermo Izquierdo, Celia Oreja-Guevara, Francisco Gascon-Gimenez, Susana Sainz de la Maza, Paulette E. Walo-Delgado, Paloma Lapuente-Suanzes, Aleksandra Maceski, Eulalia Rodriguez-Martin, Ernesto Roldan, Noelia Villarrubia, Albert Saiz, Yolanda Blanco, Carolina Diaz-Perez, Gabriel Valero-Lopez, Judit Diaz-Diaz, Yolanda Aladro, Luis Brieva, Cristina Iniguez, Ines Gonzalez-Suarez, Luis A. Rodriguez de Antonio, Jose M. Garcia-Dominguez, Julia Sabin, Sara Llufriu, Jaime Masjuan, Lucienne Costa-Frossard, Luisa M. Villar
Summary: This study aimed to investigate the role of inflammation in the response to ocrelizumab in patients with PPMS. The findings showed that over 60% of patients achieved no evidence of disease activity (NEDA) after one year of treatment, regardless of their baseline characteristics. The baseline inflammation influenced the predominant immunological pathways, with inflammatory B cells playing a pivotal role in Gd+ patients and inflammatory T and innate immune cells in Gd- patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Jia Liu, Chi Zhang, Yao Xie, Li Zhou, Li Guo, Bin Li, Zhen Jia, Jingze Zhang, Kazuo Sugimoto, Ying Gao
Summary: DATE-TCM is the first, largest, most geographically extensive, and standard registry-based observational study that systematically document the real-world data regarding the TCM application in the DDC populations. It aims to clarify the comprehensive characteristics and outcomes of TCM in DDC, further shed light on standardizing and optimizing the TCM measures for DDC management, and establishing evidence-based clinical practice guidelines for TCM application in DDC.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Rehabilitation
Ana Torres-Costoso, Vicente Martinez-Vizcaino, Sara Reina-Gutierrez, Celia Alvarez-Bueno, Maria Jose Guzman-Pavon, Diana P. Pozuelo-Carrascosa, Ruben Fernandez-Rodriguez, Mairena Sanchez-Lopez, Ivan Cavero-Redondo
Summary: This study conducted a network meta-analysis to determine the positive influence of physical exercise on multiple sclerosis fatigue, with combined exercise and resistance training showing the most significant effects on fatigue improvement, particularly in physical and total fatigue. Exercise should be considered an effective strategy in managing fatigue among individuals with MS.
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
(2022)
Article
Multidisciplinary Sciences
Irene Molina-Gonzalez, Rebecca K. Holloway, Zoeb Jiwaji, Owen Dando, Sarah A. Kent, Katie Emelianova, Amy F. Lloyd, Lindsey H. Forbes, Ayisha Mahmood, Thomas Skripuletz, Viktoria Gudi, James A. Febery, Jeffrey A. Johnson, Jill H. Fowler, Tanja Kuhlmann, Anna Williams, Siddharthan Chandran, Martin Stangel, Andrew J. M. Howden, Giles E. Hardingham, Veronique E. Miron
Summary: Failed regeneration of myelin around neuronal axons following central nervous system damage contributes to nerve dysfunction and clinical decline in various neurological conditions. This study shows that the interaction between astrocytes and mature myelin-forming oligodendrocytes is crucial for remyelination. Astrocytes support the survival of regenerating oligodendrocytes by downregulating the Nrf2 pathway and activating the cholesterol biosynthesis pathway. This discovery reveals a drug strategy for central nervous system regeneration by targeting the astrocyte-oligodendrocyte interaction.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Annarita Del Gatto, Michele Saviano, Laura Zaccaro
Summary: Multiple sclerosis is a progressive and highly debilitating disease, with current treatment strategies showing limitations in preventing disease progression. Peptide-based systems offer new therapeutic opportunities for the treatment of MS.
Article
Endocrinology & Metabolism
Ravindran Vini, Arumugam Rajavelu, Sreeja Sreeharshan
Summary: 27-HC, the first known endogenous selective estrogen receptor modulator, is closely associated with breast cancer. This study reveals that 27-HC may induce aberrant DNA methylation changes on gene promoters through modulating the ER-alpha and DNMT3B complexes, thereby affecting drug responses and breast cancer development.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemical Research Methods
Eline B. A. van den Berg, Jaap C. W. Hendriks, Everdine W. Elsinga, Mark Eggink, Eef H. C. Dirksen
Summary: Antibody-drug conjugates (ADCs) are a promising class of oncology therapeutics that can deliver cytotoxic drugs to specific locations. This study investigated the impact of disulfide bond reduction time on drug load and isomers of ADCs, revealing a dynamic relationship between them.
Article
Biochemistry & Molecular Biology
Na Zhan, Boyang Wang, Nikita Martens, Yankai Liu, Shangge Zhao, Gardi Voortman, Jeroen Van Rooij, Frank Leijten, Tim Vanmierlo, Folkert Kuipers, Johan W. Jonker, Vincent W. Bloks, Dieter Luetjohann, Marcella Palumbo, Francesca Zimetti, Maria Pia Adorni, Hongbing Liu, Monique T. Mulder
Summary: The study identified five novel LXR-activating 24-oxidized sterols with potential therapeutic applications in neurodegenerative and cardiovascular diseases. These compounds demonstrated high potency for LXR alpha/beta activation and induced the expression of LXR-target genes involved in cellular cholesterol turnover. They also enhanced cholesterol efflux and upregulated the production of endogenous LXR agonists. Overall, these findings suggest the potential of developing compounds targeting LXR for the treatment of lipid-related diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Suzanne A. E. van Wouw, Marlene van den Berg, Maroua El Ouraoui, Amber Meurs, Jenina Kingma, Roelof Ottenhoff, Melanie Loix, Marten A. Hoeksema, Koen Prange, Gerard Pasterkamp, Jerome J. A. Hendriks, Jeroen F. J. Bogie, Jan B. van Klinken, Frederic M. Vaz, Aldo Jongejan, Menno P. J. de Winther, Noam Zelcer
Summary: LXR transcription factors play an important role in regulating the composition of lipid species in cellular membranes, particularly lysoplasmalogens. This study identified TMEM86a as a sterol-regulated lysoplasmalogenase in macrophages, which contributes to sterol-dependent membrane remodeling. TMEM86a has been found to have lysoplasmalogenase activity and its overexpression reduces lysoplasmalogen abundance and membrane fluidity in macrophages.
JOURNAL OF LIPID RESEARCH
(2023)
Article
Multidisciplinary Sciences
Niamh B. B. McNamara, David A. D. Munro, Nadine Bestard-Cuche, Akiko Uyeda, Jeroen F. J. Bogie, Alana Hoffmann, Rebecca K. K. Holloway, Irene Molina-Gonzalez, Katharine E. E. Askew, Stephen Mitchell, William Mungall, Michael Dodds, Carsten Dittmayer, Jonathan Moss, Jamie Rose, Stefan Szymkowiak, Lukas Amann, Barry W. W. McColl, Marco Prinz, Tara L. L. Spires-Jones, Werner Stenzel, Karen Horsburgh, Jerome J. A. Hendriks, Clare Pridans, Rieko Muramatsu, Anna Williams, Josef Priller, Veronique E. E. Miron
Summary: This study reveals the crucial role of resident microglia in maintaining myelin health in the central nervous system. Microglia are involved in regulating myelin growth, preserving myelin integrity, and influencing cognitive function. Disruption of the TGF beta 1-TGF beta R1 axis is implicated in the mechanism underlying the loss of myelin health. The findings suggest that targeting microglia could be a potential therapeutic approach for conditions with dysregulated myelin growth and integrity.
Editorial Material
Cell Biology
Philippos Koulousakis, Assia Tiane, Niels Hellings, Jos Prickaerts, Daniel van den Hove, Tim Vanmierlo
NEURAL REGENERATION RESEARCH
(2023)
Article
Immunology
Melissa Schepers, Dean Paes, Assia Tiane, Ben Rombaut, Elisabeth Piccart, Lieve van Veggel, Pascal Gervois, Esther Wolfs, Ivo Lambrichts, Chiara Brullo, Olga Bruno, Ernesto Fedele, Roberta Ricciarelli, Charles Ffrench-Constant, Marie E. Bechler, Pauline van Schaik, Wia Baron, Evy Lefevere, Kobi Wasner, Anne Grunewald, Catherine Verfaillie, Paulien Baeten, Bieke Broux, Paul Wieringa, Niels Hellings, Jos Prickaerts, Tim Vanmierlo
Summary: Multiple sclerosis (MS) is a chronic autoimmune disease characterized by central nervous system inflammation and demyelination. Current therapies are insufficient in halting or reversing disease progression. This study shows that selective inhibition of phosphodiesterase 4 (PDE4) promotes myelin repair and reduces inflammation. Inhibition of PDE4D enhances (re)myelination, while inhibition of PDE4B exerts anti-inflammatory effects. These findings suggest that gene specific PDE4 inhibitors could be potential therapeutic agents for MS.
BRAIN BEHAVIOR AND IMMUNITY
(2023)
Article
Pharmacology & Pharmacy
Melissa Schepers, Afonso Malheiro, Adrian Seijas Gamardo, Niels Hellings, Jos Prickaerts, Lorenzo Moroni, Tim Vanmierlo, Paul Wieringa
Summary: Phosphodiesterase 4 (PDE4) inhibitors, such as roflumilast, have been extensively studied for their anti-inflammatory and neuroregenerative properties. This study found that roflumilast can promote differentiation of Schwann cells and accelerate myelination, as demonstrated in vitro using rat cells and a 3D co-culture model. These findings contribute to the development of PDE4 inhibition-based therapies in peripheral regenerative medicine.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Tim Vangansewinkel, Stefanie Lemmens, Assia Tiane, Nathalie Geurts, Dearbhaile Dooley, Tim Vanmierlo, Gunnar Pejler, Sven Hendrix
Summary: In this study, researchers investigated the therapeutic potential of recombinant mMCP6 in improving functional outcomes after spinal cord injury. The findings suggest that mMCP6 can enhance recovery by reducing astrogliosis and promoting (re)myelination in the injured spinal cord.
Review
Biochemistry & Molecular Biology
Femke Mussen, Jana Van Broeckhoven, Niels Hellings, Melissa Schepers, Tim Vanmierlo
Summary: Traumatic spinal cord injury (SCI) is characterized by severe neuroinflammation and hampered neuroregeneration. Current therapies have limited effectiveness, so new strategies targeting the initial inflammatory reactions and promoting endogenous repair are crucial. Adenosine monophosphate (cAMP) regulates these processes and inhibiting its hydrolyzing enzyme phosphodiesterase (PDE) has shown promise in modulating inflammation and promoting regeneration. This review focuses on the immunomodulatory and neuroregenerative role of cAMP-specific PDE inhibition in SCI.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell & Tissue Engineering
David Diouf, Maria Rosaria Vitale, Johanna Eva Maria Zoeller, Ana -Magdalena Pineau, Eva Klopocki, Catharina Hamann, Georg Christoph Ziegler, Tim Vanmierlo, Daniel Van den Hove, Klaus-Peter Lesch
Summary: Fibroblasts from a healthy individual were infected with a Sendai virus to produce transgene-free human induced pluripotent stem cells (iPSCs) containing the Yamanaka factors. CRISPR/Cas9 was used to create an isogenic cell line with an inactivated ST3GAL3 gene, which is associated with neurodevelopmental and psychiatric disorders. This ST3GAL3 null mutant (ST3GAL3-/-) iPSC line, with pluripotency-associated marker expression, ability to differentiate into three germ layers in vitro, and normal karyotype, provides a powerful tool to study the impact of deficient glycoprotein sialylation in neural development and plasticity.
STEM CELL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Ellis Nelissen, Melissa Schepers, Laura Ponsaerts, Sebastien Foulquier, Annelies Bronckaers, Tim Vanmierlo, Peter Sandner, Jos Prickaerts
Summary: Vascular cognitive impairment (VCI) is a neurodegenerative disorder characterized by a vascular component, involving decreased cerebral blood flow, white matter lesions, endothelial dysfunction, and blood-brain barrier impairments. Oxidative stress and inflammation are major underlying mechanisms. Modulation of soluble guanylate cyclase (sGC) activity can improve vascular and neural function, and has shown efficacy in cardiovascular diseases.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Nutrition & Dietetics
Nikita Martens, Na Zhan, Gardi Voortman, Frank P. J. Leijten, Connor van Rheenen, Suzanne van Leerdam, Xicheng Geng, Michiel Huybrechts, Hongbing Liu, Johan W. W. Jonker, Folkert Kuipers, Dieter Lutjohann, Tim Vanmierlo, Monique T. T. Mulder
Summary: The nuclear liver X receptors (LXRα/β) and peroxisome proliferator-activated receptors (PPARα/γ) play a role in regulating lipid metabolism and inflammation. The activation of these receptors has neuroprotective effects and may be a potential treatment for neurodegenerative disorders like Alzheimer's Disease (AD). The brown seaweed Sargassum fusiforme contains compounds that activate these receptors and have been shown to prevent disease progression in a mouse model of AD.
Article
Cell Biology
Alessandra Roggeri, Guendalina Olivero, Cesare Usai, Tim Vanmierlo, Anna Pittaluga
Summary: This study provides evidence of the existence and distribution of inhibitory S1P1R and facilitatory S1P3R in cortical nerve endings of healthy mice. It also shows that the activity of these receptors is amplified in mice with experimental autoimmune encephalomyelitis (EAE) but can be recovered after chronic FTY720 treatment.
Meeting Abstract
Medicine, Research & Experimental
Ellis Nelissen, Tim Vanmierlo, Peter Sandner, Jos Prickaerts
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Meeting Abstract
Medicine, Research & Experimental
Jos Prickaerts, Ellis Nelissen, Tim Vanmierlo, Peter Sandner
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
