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| Open AccessAssociations of myeloid cells with cellular and humoral responses following vaccinations in patients with neuroimmunological diseases
Patients with autoimmune diseases require immunosuppressive treatments that affect their responses to infection and vaccination. Here, using mass cytometry, the authors to identify a role for myeloid cells in cellular and humoral responses following vaccination against SARS-CoV-2 in patients with neuroimmunological diseases.
- Meng Wang
- , Adeline Dehlinger
- & Chotima Böttcher
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Article
| Open AccessHematopoietic stem-cell gene therapy is associated with restored white matter microvascular function in cerebral adrenoleukodystrophy
Cerebral adrenoleukodystrophy (CALD) is a demyelinating disease caused by loss of ABCD1 gene function. Here the authors investigate white matter structural and microvascular changes in boys with CALD that received gene therapy with autologous hematopoietic stem-cells.
- Arne Lauer
- , Samantha L. Speroni
- & Patricia L. Musolino
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Article
| Open AccessAndrogens show sex-dependent differences in myelination in immune and non-immune murine models of CNS demyelination
Androgen effects have been poorly studied in demyelinating diseases in females. Here, authors show androgen requirement for proper myelin regeneration in females and the critical need to consider male-female differences in multiple sclerosis patients.
- Amina Zahaf
- , Abdelmoumen Kassoussi
- & Elisabeth Traiffort
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Article
| Open AccessIdentifying multiple sclerosis subtypes using unsupervised machine learning and MRI data
Multiple sclerosis is a heterogeneous progressive disease. Here, the authors use an unsupervised machine learning algorithm to determine multiple sclerosis subtypes, progression, and response to potential therapeutic treatments based on neuroimaging data.
- Arman Eshaghi
- , Alexandra L. Young
- & Olga Ciccarelli
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Article
| Open AccessModulation of proteoglycan receptor PTPσ enhances MMP-2 activity to promote recovery from multiple sclerosis
Demyelination failure in multiple sclerosis (MS) may contribute to the disease progression. This study shows that chondroitin sulfate proteoglycans (CSPGs) can inhibit remyelination in an animal model of MS via CSPG binding with the receptor PTPσ on oligodendrocyte progenitor cells, and disruption of this interaction can promote recovery in the animal models of MS.
- Fucheng Luo
- , Amanda Phuong Tran
- & Yan Yang
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Article
| Open AccessA whole-genome sequence study identifies genetic risk factors for neuromyelitis optica
Neuromyelitis optica (NMO) is a rare autoimmune condition characterized by inflammation and demyelination of the optic nerve and the spinal cord. Here, Estrada et al. identify NMO susceptibility variants in the MHC region and find that autoantibody-positive NMO genetically overlaps with lupus.
- Karol Estrada
- , Christopher W. Whelan
- & Daniel G. MacArthur
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Article
| Open AccessCirculating exosomes suppress the induction of regulatory T cells via let-7i in multiple sclerosis
MiRNAs are small RNA molecules that can regulate gene expression. Here the authors show that expression of several exosomal miRNAs are altered in patients with multiple sclerosis, and that let-7i modulates regulatory T cell homeostasis to contribute to pathogenesis.
- Kimitoshi Kimura
- , Hirohiko Hohjoh
- & Takashi Yamamura
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Article
| Open AccessTransient auditory nerve demyelination as a new mechanism for hidden hearing loss
Hidden hearing loss (HHL) is an auditory neuropathy that impairs one’s ability to hear, particularly in a noisy environment. Here the authors show that in mice, transient loss of cochlear Schwann cells results in permanent disruption of the cochlear heminodal structure, leading to auditory deficits characteristic of HHL.
- Guoqiang Wan
- & Gabriel Corfas
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Article
| Open AccessStructural basis of myelin-associated glycoprotein adhesion and signalling
Myelin-associated glycoprotein (MAG) maintains myelin-axon spacing. Here, the authors report the crystal structures of the MAG full ectodomain in complex with oligosaccharide, and use additional assays to provide insights into the mechanism of MAG-mediated signalling.
- Matti F. Pronker
- , Suzanne Lemstra
- & Bert J. C. Janssen
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Article
| Open Access25-hydroxycholesterol contributes to cerebral inflammation of X-linked adrenoleukodystrophy through activation of the NLRP3 inflammasome
The mechanism underlying neuroinflammation in X-linked adrenoleukodystrophy (ALD) is poorly understood. Here authors identify aberrant production of 25-hydroxycholesterol (25-HC) in ALD patient-derived cells, and show that 25-HC mediates neuroinflammation via activating the NLRP3 inflammasome.
- Jiho Jang
- , Sangjun Park
- & Dong-Wook Kim
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Article
| Open AccessThe Lin28/let-7 axis is critical for myelination in the peripheral nervous system
MicroRNAs are known to regulate myelination in the peripheral nervous system, but the underlying mechanisms remain unclear. Here the authors show that the Lin28B/let-7 axis drives the onset of myelination by promoting Krox20 expression through suppression of Notch signalling.
- Deniz Gökbuget
- , Jorge A. Pereira
- & Ueli Suter
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Article
| Open AccessdNP2 is a blood–brain barrier-permeable peptide enabling ctCTLA-4 protein delivery to ameliorate experimental autoimmune encephalomyelitis
Most of the cell penetrating peptides can transport therapeutic agents across plasma membranes but barely across the blood-brain barrier. Here the authors develop a peptide that can enter the brain, and show that its fusion to immunomodulatory protein ctCTLA-4 is effective in a mouse model of multiple sclerosis.
- Sangho Lim
- , Won-Ju Kim
- & Je-Min Choi
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Article
| Open AccessPharmaceutical integrated stress response enhancement protects oligodendrocytes and provides a potential multiple sclerosis therapeutic
Current multiple sclerosis treatments focus on prevention of immune attack on oligodendrocytes and myelin. Here the authors show a different strategy to ameliorate disease in several mouse models, protecting oligodendrocytes from inflammation-induced death with an FDA-approved drug, guanabenz.
- Sharon W. Way
- , Joseph R. Podojil
- & Brian Popko
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Article |
An intestinal commensal symbiosis factor controls neuroinflammation via TLR2-mediated CD39 signalling
Polysaccharide A (PSA) from the human intestinal commensal Bacteroides fragilis mediates protection against the experimental autoimmune encephalomyelitis in mice. Here, Wang et al. show that the protective function of PSA is exerted through its action on CD39+regulatory CD4 T cells via Toll-like receptor 2 signalling.
- Yan Wang
- , Kiel M. Telesford
- & Lloyd H. Kasper
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Article
| Open AccessEXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia
The exosome is responsible for mRNA degradation, which is an important step in the regulation of gene expression. Here the authors report that homozygous missense mutations in the exosome subunit, EXOSC8, may cause neurodegenerative disease in infants through the dysregulation of myelin expression.
- Veronika Boczonadi
- , Juliane S. Müller
- & Rita Horvath
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Article
| Open AccessFibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation
Multiple sclerosis is characterized by the activation of microglia cells. Davalos et al. investigate the early stages of neuroinflammation in mice and reveal that the plasma protein fibrinogen induces microglial clustering around the brain vasculature, which facilitates lesion formation and focal axonal damage.
- Dimitrios Davalos
- , Jae Kyu Ryu
- & Katerina Akassoglou