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Pathogenic inflammation in the CNS of mice carrying human PLP1 mutations.
Groh, Janos; Friedman, Hana C; Orel, Nadiya; Ip, Chi Wang; Fischer, Stefan; Spahn, Irene; Schäffner, Erik; Hörner, Michaela; Stadler, David; Buttmann, Mathias; Varallyay, Csanad; Solymosi, László; Sendtner, Michael; Peterson, Alan C; Martini, Rudolf.
Afiliación
  • Groh J; Department of Neurology, Section of Developmental Neurobiology, University Hospital Wuerzburg, D-97080 Wuerzburg, Germany.
  • Friedman HC; Laboratory of Developmental Biology, Ludmer Research and Training Building, McGill University, Montreal, QC, Canada.
  • Orel N; Institute of Clinical Neurobiology, University of Wuerzburg, Wuerzburg, Germany.
  • Ip CW; Department of Neurology, Section of Developmental Neurobiology, University Hospital Wuerzburg, D-97080 Wuerzburg, Germany.
  • Fischer S; Department of Neurology, Section of Developmental Neurobiology, University Hospital Wuerzburg, D-97080 Wuerzburg, Germany.
  • Spahn I; Department of Neurology, Section of Developmental Neurobiology, University Hospital Wuerzburg, D-97080 Wuerzburg, Germany.
  • Schäffner E; Department of Neurology, Section of Developmental Neurobiology, University Hospital Wuerzburg, D-97080 Wuerzburg, Germany.
  • Hörner M; Department of Neurology, Section of Developmental Neurobiology, University Hospital Wuerzburg, D-97080 Wuerzburg, Germany.
  • Stadler D; Department of Neurology, Section of Developmental Neurobiology, University Hospital Wuerzburg, D-97080 Wuerzburg, Germany.
  • Buttmann M; Department of Neurology, Multiple Sclerosis and Neuroimmunology, University Hospital Wuerzburg, Wuerzburg, Germany.
  • Varallyay C; Division of Neuroradiology, University Hospital Wuerzburg, Wuerzburg, Germany.
  • Solymosi L; Division of Neuroradiology, University Hospital Wuerzburg, Wuerzburg, Germany.
  • Sendtner M; Institute of Clinical Neurobiology, University of Wuerzburg, Wuerzburg, Germany.
  • Peterson AC; Laboratory of Developmental Biology, Ludmer Research and Training Building, McGill University, Montreal, QC, Canada.
  • Martini R; Department of Neurology, Section of Developmental Neurobiology, University Hospital Wuerzburg, D-97080 Wuerzburg, Germany.
Hum Mol Genet ; 25(21): 4686-4702, 2016 11 01.
Article en En | MEDLINE | ID: mdl-28173160
Progressive forms of multiple sclerosis lead to chronic disability, substantial decline in quality of life and reduced longevity. It is often suggested that they occur independently of inflammation. Here we investigated the disease progression in mouse models carrying PLP1 point mutations previously found in patients displaying clinical features of multiple sclerosis. These mouse models show loss-of-function of PLP1 associated with neuroinflammation; the latter leading to clinically relevant axonal degeneration, neuronal loss and brain atrophy as demonstrated by inactivation of the recombination activating gene 1. Moreover, these pathological hallmarks were substantially amplified when we attenuated immune regulation by inactivation of the programmed cell death-1 gene. Our observations support the view that primary oligodendroglial abnormalities can evoke pathogenically relevant neuroinflammation that drives neurodegeneration, as observed in some forms of multiple sclerosis but also in other, genetically-mediated neurodegenerative disorders of the human nervous system. As many potent immunomodulatory drugs have emerged during the last years, it is tempting to consider immunomodulation as a treatment option not only for multiple sclerosis, but also for so far non-treatable, genetically-mediated disorders of the nervous system accompanied by pathogenic neuroinflammation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína Proteolipídica de la Mielina / Esclerosis Múltiple / Mutación Tipo de estudio: Prognostic_studies Aspecto: Patient_preference Límite: Animals / Female / Humans / Male Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2016 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína Proteolipídica de la Mielina / Esclerosis Múltiple / Mutación Tipo de estudio: Prognostic_studies Aspecto: Patient_preference Límite: Animals / Female / Humans / Male Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2016 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido