Review
Immunology
Emily Kamma, Wendy Lasisi, Cole Libner, Huah Shin Ng, Jason R. Plemel
Summary: There are limited treatment options available for progressive multiple sclerosis (MS) due to a poor understanding of its pathophysiology. Microglia and macrophages play a vital role in the progressive phase of MS and may contribute to neurodegeneration. However, there is a lack of disease-modifying drugs that target these cells specifically in progressive MS.
JOURNAL OF NEUROINFLAMMATION
(2022)
Review
Neurosciences
Lindsey H. Forbes, Veronique E. Miron
Summary: Aging and progression of neurodegenerative disorders lead to remyelination failure and axonal dysfunction; CNS macrophages play a key role in remyelination, with the contribution of monocyte-derived macrophages remaining not fully understood; Recent tools have enabled the distinction between macrophage populations, shedding light on the importance of monocytes in remyelination.
Review
Immunology
Hans-Peter Hartung, Bruce A. C. Cree, Michael Barnett, Sven G. Meuth, Amit Bar-Or, Lawrence Steinman
Summary: Disease-modifying therapies for relapsing multiple sclerosis reduce relapse rates by suppressing peripheral immune cells but have limited efficacy in progressive forms of the disease. Cladribine and sphingosine 1-phosphate receptor modulators could have beneficial direct central nervous system properties.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Clinical Neurology
Effrosyni Koutsouraki, Koukoulidis Theodoros, Georgiadou Eleni, Kalampouka Marianna, Nikolaidou Areti, Koukoulidou Ariadni, Michmizos Dimitrios
Summary: Multiple sclerosis (MS) is a chronic progressive disease affecting both the central nervous system (CNS) and autonomic nervous system (ANS), leading to a range of urological, sexual, gastrointestinal, cardiovascular, and thermoregulatory disorders as well as increased fatigue. The manifestations of ANS dysfunction in MS are often underestimated due to the non-specificity of symptoms and limited evaluation in clinical practice. The underlying mechanisms causing these disorders have yet to be fully investigated, hindering targeted etiological treatment. Early diagnosis and individualized treatment regimens, incorporating multiple approaches, have shown the best results in managing ANS dysfunction in MS patients.
JOURNAL OF NEUROLOGY
(2023)
Article
Pharmacology & Pharmacy
Wan-Jiao Gao, Jian-Xin Liu, Yie Xie, Pei Luo, Zhong-Qiu Liu, Liang Liu, Hua Zhou
Summary: A large number of macrophages in inflamed sites can exacerbate inflammatory responses, while Sinomenine can exert its anti-inflammatory effects by inhibiting macrophage migration. Sinomenine can also alleviate inflammation and prevent macrophage infiltration.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Clinical Neurology
Bardia Nourbakhsh, Christian Cordano, Carlo Asteggiano, Klemens Ruprecht, Carolin Otto, Alice Rutatangwa, Allysa Lui, Janace Hart, Eoin P. Flanagan, Judith A. James, Emmanuelle Waubant
Summary: In children with EBV seronegativity, a higher percentage have MOG antibodies, leading to a reconsideration of the diagnosis of MS. Clinicians should consider MOG-antibody disease as an alternative diagnosis to MS in children presenting with MS-like symptoms.
ANNALS OF NEUROLOGY
(2021)
Review
Cell Biology
Zhiyuan Ning, Ying Liu, Daji Guo, Wei-Jye Lin, Yamei Tang
Summary: This article reviews the basic knowledge of NK cell biology and recent advances in their roles in the healthy CNS and pathological conditions. The authors highlight the interactions between NK cells and diverse cell types in the CNS, as well as the potential value of NK cells as novel therapeutic targets for CNS diseases.
CELL COMMUNICATION AND SIGNALING
(2023)
Review
Nutrition & Dietetics
Bangqi Wang, Tianshu Fang, Hongping Chen
Summary: Zinc (Zn2+) is a crucial trace element in the human body, playing a critical role in various physiological processes. It is necessary for cellular proliferation, transcription, apoptosis, growth, immunity, and wound healing. Maintaining zinc homeostasis is vital for the central nervous system, where zinc is abundantly distributed and accumulates in presynaptic vesicles. Synaptic zinc is necessary for neural transmission and is involved in neurogenesis, cognition, memory, and learning. Disruption of zinc homeostasis is associated with several central nervous system disorders, including Alzheimer's disease, depression, Parkinson's disease, multiple sclerosis, schizophrenia, epilepsy, and traumatic brain injury. This review explores the correlation between zinc and these disorders, providing potential mechanisms and new insights for prevention and treatment.
Article
Biochemistry & Molecular Biology
Alicia Weier, Michael Enders, Philipp Kirchner, Arif Ekici, Marc Bigaud, Christopher Kapitza, Juergen Woerl, Stefanie Kuerten
Summary: Multiple sclerosis is an autoimmune disease of the central nervous system. Siponimod, the only approved drug for secondary progressive MS, acts on the peripheral immune system and does not have pronounced direct neuroprotective effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Clinical Neurology
Ivan Adamec, Magdalena Krbot Skoric, Mario Habek
Summary: Multiple sclerosis (MS) is traditionally considered a disease of the central nervous system (CNS), but emerging evidence suggests that it also affects the peripheral nervous system (PNS). Studies have shown signs of demyelination and functional involvement in the PNS of individuals with MS, particularly in the autonomic nervous system (ANS). Further research is needed to fully understand the frequency and significance of PNS involvement in MS.
NEUROLOGICAL SCIENCES
(2021)
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)
Article
Medicine, Research & Experimental
Laura Ghezzi, Bryan Bollman, Luca De Feo, Laura Piccio, Bruce D. Trapp, Robert E. Schmidt, Anne H. Cross
Summary: Multiple sclerosis (MS) is a CNS demyelinating disease that often leads to unsuccessful remyelination and neuronal/axonal damage. While oligodendroglial cells are responsible for myelin production, remyelination by Schwann cells (SchC) has been observed in spinal cord demyelination. This study investigated the extent of SchC remyelination in the brain and spinal cords of autopsied MS specimens.
LABORATORY INVESTIGATION
(2023)
Article
Cell Biology
Lydia Ayanwuyi, Nataliya Tokarska, Nikki McLean, Jayne Johnston, Valerie Verge
Summary: Brief electrical nerve stimulation has been shown to have a positive effect on the repair of demyelinating diseases and nerve injuries. It promotes the polarization of macrophages to a pro-repair phenotype, reduces inflammation, increases the number of oligodendroglial lineage cells, elevates myelin protein levels, and enhances phosphorylated neurofilaments to protect axons.
NEURAL REGENERATION RESEARCH
(2022)
Review
Cell Biology
Di Wu, Dahai Liu, Kensuke Tateishi, Fei Qi, Fang Yang, Chao Ke, Hua You
Summary: This review article presents the phenotypic and genotypic features of primary central nervous system lymphoma (PCNSL) tumor cells, and compiles the preclinical animal models of PCNSL. Researchers hope that these animal models will enhance the understanding of the molecular pathogenesis of PCNSL and accelerate the development of novel therapeutic strategies.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Review
Immunology
Yun Sun, Yankai Wen, Luxi Wang, Liang Wen, Wendong You, Shuang Wei, Lin Mao, Hao Wang, Zuobing Chen, Xiaofeng Yang
Summary: IL-33, acting through its receptor complex involving ST2 and IL-1RAP, plays crucial roles in the CNS and is implicated in the pathogenesis of various diseases. Understanding the functional roles and cellular signaling mechanisms of IL-33 in the CNS may lead to the development of diagnostic and therapeutic strategies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Mohammed A. A. Saleh, Elizabeth C. M. de Lange
Summary: This study investigated the impact of altered cerebral blood flow, tight junction paracellular pore radius, brain extracellular fluid volume, and pH values on drug transport and concentrations in the central nervous system. The results showed drug-dependent effects of pathophysiological changes on blood-brain barrier transport and drug concentrations within the brain extracellular and intracellular fluid. Changes in pore radius, pH values, and blood flow affected the rate and extent of drug transport, highlighting the importance of considering these factors in drug delivery to the brain.
Review
Hematology
Sanny Scheffer, Dorien M. A. Hermkens, Louise van der Weerd, Helga E. de Vries, Mat J. A. P. Daemen
Summary: Alzheimer's disease is characterized by neurodegeneration, neuroinflammation, and cognitive decline. Cardiovascular disease has been identified as an important contributor to the development and progression of AD, known as the vascular hypothesis. Vascular risk factors are associated with an increased chance of developing AD, with chronic cerebral hypoperfusion suggested to play a key role in disease onset.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Wieke M. van Oostveen, Elizabeth C. M. de Lange
Summary: This review discusses the contemporary methods of early diagnosis and longitudinal monitoring of AD using imaging techniques, examining their diagnostic utility, benefits, and limitations. Additionally, it assesses novel techniques, applications, and biomarkers for AD research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Nienke M. de Wit, Kevin Mol, Sabela Rodriguez-Lorenzo, Helga E. de Vries, Gijs Kooij
Summary: Alzheimer's disease is the leading cause of dementia worldwide, characterized by extracellular amyloid deposition, neurofibrillary tangles, and chronic neuroinflammation. There is currently no cure for prevention of Alzheimer's disease, but manipulating bioactive lipid pathways may offer novel therapeutic approaches to resolve chronic neuroinflammation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Clinical Neurology
Ynn van Olst, Carla Rodriguez-Mogeda, Carmen Picon, Svenja Kiljan, Rachel E. James, Alwin Kamermans, Susanne M. A. van der Pol, Lydian Knoop, Iliana Michailidou, Evelien Drost, Marc Franssen, Geert J. Schenk, Jeroen J. G. Geurts, Sandra Amor, Nicholas D. Mazarakis, Jack van Horssen, Helga E. de Vries, Richard Reynolds, Maarten E. Witte
Summary: The study identified two distinct microglial populations, MS1 and MS2, in the cortex of progressive MS patients, which differentially associate with neurodegeneration. Results suggest that microglia may initially protect neurons from meningeal inflammation-induced cell death by regulating synaptic location and phagocytosis, but over time, this protective property may be lost.
ACTA NEUROPATHOLOGICA
(2021)
Article
Pharmacology & Pharmacy
David Roig-Carles, Eduard Willms, Ruud D. Fontijn, Sarai Martinez-Pacheco, Imre Mager, Helga E. de Vries, Mark Hirst, Basil Sharrack, David K. Male, Cheryl A. Hawkes, Ignacio A. Romero
Summary: It has been discovered that small EVs released by inflamed brain endothelial cells may contribute to blood-brain barrier dysfunction, leading to cerebrovascular disorders. The expression of VCAM1 is associated with T-cell adhesion, while ICAM1 does not affect this process.
Review
Biochemistry & Molecular Biology
Merel Rijnsburger, Niek Djuric, Inge A. Mulder, Helga E. de Vries
Summary: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, with significant impact on patients and their proxies. Obesity is associated with an increased risk of developing MS. Adipokines play a crucial role in MS pathology and may have therapeutic potential in targeting neuroinflammation and neurodegeneration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Geriatrics & Gerontology
Sandra den Hoedt, Simone M. Crivelli, Frank P. J. Leijten, Mario Losen, Jo A. A. Stevens, Marina Mane-Damas, Helga E. de Vries, Jochen Walter, Mina Mirzaian, Eric J. G. Sijbrands, Johannes M. F. G. Aerts, Adrie J. M. Verhoeven, Pilar Martinez-Martinez, Monique T. Mulder
Summary: The study found that sex is a stronger determinant of brain ceramide levels in mice than APOE genotype, AD background, or age. Whether these differences impact AD neuropathology in men and women remains to be investigated.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Review
Geriatrics & Gerontology
Antia Custodia, Alberto Ouro, Daniel Romaus-Sanjurjo, Juan Manuel Pias-Peleteiro, Helga E. de Vries, Jose Castillo, Tomas Sobrino
Summary: Alzheimer's disease is a neurodegenerative disease with a complex and unknown etiology. The two-hit vascular hypothesis suggests that brain vascular damage leads to the accumulation of beta-amyloid protein. Research has shown that endothelial progenitor cells play a significant role in understanding the disease etiology and developing potential therapies.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Cell Biology
Haoxiao Zuo, Marie-Jose C. Van Lierop, Jorn Kaspers, Remco Bos, Anneke Reurs, Saheli Sarkar, Tania Konry, Alwin Kamermans, Gijs Kooij, Helga E. de Vries, Tanja D. de Gruijl, Alex Karlsson-Parra, Erik H. Manting, Ada M. Kruisbeek, Satwinder Kaur Singh
Summary: DCP-001 is a cell-based cancer vaccine that has been shown to be safe and feasible as a post-remission therapy in acute myeloid leukemia. It works by activating and recruiting host antigen-presenting cells to capture tumor-associated antigens and stimulate tumor-reactive T-cells. The improved uptake of DCP-001 by blocking CD47 suggests potential combination therapies with CD47 blocking agents.
Article
Neurosciences
Nienke R. Wevers, Arya Lekshmi Nair, Tania M. Fowke, Maria Pontier, Dhanesh G. Kasi, Xandor M. Spijkers, Charlie Hallard, Gwenaelle Rabussier, Remko van Vught, Paul Vulto, Helga E. de Vries, Henriette L. Lanz
Summary: The study introduces a human NVU on-a-chip model that mimics ischemic stroke, offering potential applications in NVU function research and drug screening. Key findings include insights into brain endothelial cells and neuronal function within the model, highlighting its potential for further investigations in neurological disorders.
FLUIDS AND BARRIERS OF THE CNS
(2021)
Review
Neurosciences
I. A. Mulder, E. T. van Bavel, H. E. de Vries, J. M. Coutinho
Summary: This review provides an overview of compounds tested in clinical AIS trials and gives insight into which of these drugs warrant a re-evaluation as an add-on therapy for AIS in the era of EVT. Main trial outcomes and safety issues are summarized and promising compounds for re-evaluation are highlighted. Looking at group effect, drugs intervening with oxidative and nitrosative stress and neurogenesis/-regeneration and -recovery appear to have a favourable safety profile and show the most promising results regarding efficacy.
FLUIDS AND BARRIERS OF THE CNS
(2021)
Article
Biology
Sabela Rodriguez-Lorenzo, Lynn van Olst, Carla Rodriguez-Mogeda, Alwin Kamermans, Susanne M. A. van der Pol, Ernesto Rodriguez, Gijs Kooij, Helga E. de Vries
Summary: In this study, the immune landscape of periventricular brain regions in patients with MS was analyzed using single-cell mass cytometry (CyTOF). The results showed the accumulation of CD56(bright) NK cells in the brain regions of MS patients, bringing NK cells back into the spotlight of MS pathology.
Review
Neurosciences
Parand Zarekiani, Henrique Nogueira Pinto, Elly M. Hol, Marianna Bugiani, Helga E. de Vries
Summary: The neurovascular unit (NVU) is a highly organized multicellular system in the brain, consisting of neuronal, glial, and vascular cells. Dysfunctions of the NVU occur in various neurological disorders, but little is known about its function in leukodystrophies. Human induced pluripotent stem cells (hiPSC) offer a solution to overcome the limitations of studying leukodystrophies, providing a biologically relevant human context and preserving the patient's genetic background. This review focuses on the NVU function in leukodystrophies and the use of hiPSC-derived models to study neurovascular pathophysiology in these diseases.
FLUIDS AND BARRIERS OF THE CNS
(2022)
Review
Biochemistry & Molecular Biology
Chunyuan Yin, Amy C. C. Harms, Thomas Hankemeier, Alida Kindt, Elizabeth C. M. de Lange
Summary: Alzheimer's disease is an aging-related neurodegenerative disease that leads to progressive memory loss and cognitive decline. Understanding the pathogenesis and etiology of the disease is still limited, and there are no effective treatments available. Metabolomics offers a valuable approach to studying biochemical changes and discovering potential therapeutic targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)