Journal: Acta Neuropathologica

Abbreviation

Acta Neuropathol

Publisher

Springer

Journal Volumes

ISSN

0001-6322
1432-0533

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Publications 1 - 10 of 16
  • Energy metabolism in ALS: an underappreciated opportunity?
    Item type: Journal Article
    Vandoorne, Tijs; De Bock, Katrien; Van Den Bosch, Ludo (2018)
    Acta Neuropathologica
    Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive and fatal neurodegenerative disorder that primarily affects motor neurons. Despite our increased understanding of the genetic factors contributing to ALS, no effective treatment is available. A growing body of evidence shows disturbances in energy metabolism in ALS. Moreover, the remarkable vulnerability of motor neurons to ATP depletion has become increasingly clear. Here, we review metabolic alterations present in ALS patients and models, discuss the selective vulnerability of motor neurons to energetic stress, and provide an overview of tested and emerging metabolic approaches to treat ALS. We believe that a further understanding of the metabolic biology of ALS can lead to the identification of novel therapeutic targets.
  • Spatial immune profiling of glioblastoma identifies an inflammatory, perivascular phenotype associated with longer survival
    Item type: Other Journal Item
    Wirsching, Hans-Georg; Felsberg, Jörg; Prummer, Michael; et al. (2023)
    Acta Neuropathologica
  • Single-cell profiling of myasthenia gravis identifies a pathogenic T cell signature
    Item type: Journal Article
    Ingelfinger, Florian; Krishnarajah, Sinduya; Kramer, Michael; et al. (2021)
    Acta Neuropathologica
    Myasthenia gravis (MG) is an autoimmune disease characterized by impaired neuromuscular signaling due to autoantibodies targeting the acetylcholine receptor. Although its auto-antigens and effector mechanisms are well defined, the cellular and molecular drivers underpinning MG remain elusive. Here, we employed high-dimensional single-cell mass and spectral cytometry of blood and thymus samples from MG patients in combination with supervised and unsupervised machine-learning tools to gain insight into the immune dysregulation underlying MG. By creating a comprehensive immune map, we identified two dysregulated subsets of inflammatory circulating memory T helper (Th) cells. These signature ThCD103 and ThGM cells populated the diseased thymus, were reduced in the blood of MG patients, and were inversely correlated with disease severity. Both signature Th subsets rebounded in the blood of MG patients after surgical thymus removal, indicative of their role as cellular markers of disease activity. Together, this in-depth analysis of the immune landscape of MG provides valuable insight into disease pathogenesis, suggests novel biomarkers and identifies new potential therapeutic targets for treatment.
  • Muscle biopsy findings in a new hereditary distal vacuolar myopathy associated with mutation of the nuclear matrix protein, matrin 3
    Item type: Other Conference Item
    Weis, Joachim; Krieger, Michele; Elbracht, Miriam; et al. (2009)
    Acta Neuropathologica
  • Acute function of secreted amyloid precursor protein fragment APPsα in synaptic plasticity
    Item type: Journal Article
    Hick, Meike; Herrmann, Ulrike; Weyer, Sascha W.; et al. (2015)
    Acta Neuropathologica
  • Expression pattern of NOGO-A protein in the human nervous system
    Item type: Journal Article
    Buss, A.; Sellhaus, B.; Wolmsley, A.; et al. (2005)
    Acta Neuropathologica
  • Autosomal recessive Charcot-Marie-Tooth diseases
    Item type: Other Conference Item
    Weis, J.; Schroeder, J. M.; Kruettgen, A.; et al. (2007)
    Acta Neuropathologica
  • RhoA regulates translation of the Nogo-A decoy SPARC in white matter-invading glioblastomas
    Item type: Journal Article
    Wirthschaft, Peter; Bode, Julia; Soni, Himanshu; et al. (2019)
    Acta Neuropathologica
    Glioblastomas strongly invade the brain by infiltrating into the white matter along myelinated nerve fiber tracts even though the myelin protein Nogo-A prevents cell migration by activating inhibitory RhoA signaling. The mechanisms behind this long-known phenomenon remained elusive so far, precluding a targeted therapeutic intervention. This study demonstrates that the prevalent activation of AKT in gliomas increases the ER protein-folding capacity and enables tumor cells to utilize a side effect of RhoA activation: the perturbation of the IRE1α-mediated decay of SPARC mRNA. Once translation is initiated, glioblastoma cells rapidly secrete SPARC to block Nogo-A from inhibiting migration via RhoA. By advanced ultramicroscopy for studying single-cell invasion in whole, undissected mouse brains, we show that gliomas require SPARC for invading into white matter structures. SPARC depletion reduces tumor dissemination that significantly prolongs survival and improves response to cytostatic therapy. Our finding of a novel RhoA-IRE1 axis provides a druggable target for interfering with SPARC production and underscores its therapeutic value.
  • The role of the mutated P56S VAPB protein in the autosomal dominant form of amyotrophic lateral sclerosis (ALS8)
    Item type: Other Conference Item
    Nachreiner, Thomas; Esser, M.; Senderek, Jan; et al. (2009)
    Acta Neuropathologica
  • Persistent virus-specific and clonally expanded antibody-secreting cells respond to induced self-antigen in the CNS
    Item type: Journal Article
    Agrafiotis, Andreas; Dizerens, Raphael; Vincenti, Ilena; et al. (2023)
    Acta Neuropathologica
    B cells contribute to the pathogenesis of both cellular- and humoral-mediated central nervous system (CNS) inflammatory diseases through a variety of mechanisms. In such conditions, B cells may enter the CNS parenchyma and contribute to local tissue destruction. It remains unexplored, however, how infection and autoimmunity drive transcriptional phenotypes, repertoire features, and antibody functionality. Here, we profiled B cells from the CNS of murine models of intracranial (i.c.) viral infections and autoimmunity. We identified a population of clonally expanded, antibody-secreting cells (ASCs) that had undergone class-switch recombination and extensive somatic hypermutation following i.c. infection with attenuated lymphocytic choriomeningitis virus (rLCMV). Recombinant expression and characterisation of these antibodies revealed specificity to viral antigens (LCMV glycoprotein GP), correlating with ASC persistence in the brain weeks after resolved infection. Furthermore, these virus-specific ASCs upregulated proliferation and expansion programs in response to the conditional and transient induction of the LCMV GP as a neo-self antigen by astrocytes. This class-switched, clonally expanded, and mutated population persisted and was even more pronounced when peripheral B cells were depleted prior to autoantigen induction in the CNS. In contrast, the most expanded B cell clones in mice with persistent expression of LCMV GP in the CNS did not exhibit neo-self antigen specificity, potentially a consequence of local tolerance induction. Finally, a comparable population of clonally expanded, class-switched, and proliferating ASCs was detected in the cerebrospinal fluid of relapsing multiple sclerosis (RMS) patients. Taken together, our findings support the existence of B cells that populate the CNS and are capable of responding to locally encountered autoantigens.
Publications 1 - 10 of 16