Microglial-dependent neurodegeneration in multiple sclerosis is fueled by pHERV-W envelope protein
Author(s): ,
D. Kremer
Affiliations:
Department of Neurology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
,
J. Gruchot
Affiliations:
Department of Neurology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
,
V. Weyers
Affiliations:
Department of Neurology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
,
L. Oldemeier
Affiliations:
Department of Neurology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
,
P. Göttle
Affiliations:
Department of Neurology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
,
L. Healy
Affiliations:
Montreal Neurological Institute & Hospital, McGill University, Montreal, QC, Canada
,
J.H. Jang
Affiliations:
Montreal Neurological Institute & Hospital, McGill University, Montreal, QC, Canada
,
R. Dutta
Affiliations:
Department of Neurosciences, Cleveland Clinic Foundation Lerner Research Institute, Cleveland, OH, United States
,
B. Trapp
Affiliations:
Department of Neurosciences, Cleveland Clinic Foundation Lerner Research Institute, Cleveland, OH, United States
,
H. Perron
Affiliations:
GeNeuro S.A., Geneva, Switzerland
,
H.-P. Hartung
Affiliations:
Department of Neurology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
P. Küry
Affiliations:
Department of Neurology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
ECTRIMS Online Library. Kremer D. Oct 12, 2018; 228132; P1754
David Kremer
David Kremer
Contributions
Abstract

Abstract: P1754

Type: Poster Sessions

Abstract Category: N/A

Neurodegeneration in the central nervous system (CNS) as one of the histopathological hallmarks of Multiple Sclerosis (MS) is tightly associated with clinical disability and disease progression. A large body of evidence points to the central role of microglial cells in these degenerative processes. However, the exact underlying mechanisms which drive this cell population towards a deleterious phenotype are still largely elusive. In previous studies we demonstrated that via its envelope protein Env human endogenous retrovirus type W (pHERV-W) interferes with oligodendroglial precursor cell (OPC) differentiation thereby inhibiting remyelination. Here, we now investigated how Env contributes to axonal injury in MS. We could demonstrate that Env-positive microglia are abundantly present in MS lesions adjacent to sites of axonal injury. Env-mediated activation of microglia leads to a change to ameboid cell morphology, an increased cell proliferation, an induction and excretion of proinflammatory agents, a reduced expression of neuroprotective factors and a diminished myelin clearance capacity. In addition, in Env-stimulated neuron-microglia cocultures microglia can be found in tight association with compromised axons. These findings suggest that Env-mediated modulation of microglial homeostasis fuels and contributes to axonal damage in MS promoting neurodegeneration.
Disclosure: David Kremer: nothing to disclose
Joel Gruchot: nothing to disclose
Vivien Weyers: nothing to disclose
Lisa Oldemeier: nothing to disclose
Peter Göttle: nothing to disclose
Luke Healy: nothing to disclose
Jeong Ho Jang: nothing to disclose
Ranjan Dutta: nothing to disclose
Bruce Trapp: nothing to disclose
Hervé Perron: nothing to disclose
Hans-Peter Hartung: nothing to disclose
Patrick Küry: nothing to disclose

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies