دورية أكاديمية

Molecular and celllar mechanisms underlying anti-neuronal antibody mediated disorders of the central nervous system

التفاصيل البيبلوغرافية
العنوان: Molecular and celllar mechanisms underlying anti-neuronal antibody mediated disorders of the central nervous system
المؤلفون: van Coevorden - Hameete, Marleen, de Graaff, Esther, Titulaer, M.J, Hoogenraad, Casper, Sillevis Smitt, P.A.
المساهمون: Sub Cell Biology, Cell Biology, Neurobiology and Biophysics
سنة النشر: 2014
مصطلحات موضوعية: Central nervous system, Autoimmune encephalitis, Antibody, Cell surface antigen, Neurotransmitter receptor, Ion channel
الوصف: Over the last decade multiple autoantigens located on the plasma membrane of neurons have been identified. Neuronal surface antigens include molecules directly involved in neurotransmission and excitability. Binding of the antibody to the antigen may directly alter the target protein's function, resulting in neurological disorders. The often striking reversibility of symptoms following early aggressive immunotherapy supports a pathogenic role for autoantibodies to neuronal surface antigens. In order to better understand and treat these neurologic disorders it is important to gain insight in the underlying mechanisms of antibody pathogenicity. In this review we discuss the clinical, circumstantial, in vitro and in vivo evidence for neuronal surface antibody pathogenicity and the possible underlying cellular and molecular mechanisms. This review shows that antibodies to neuronal surface antigens are often directed at conformational epitopes located in the extracellular domain of the antigen. The conformation of the epitope can be affected by specific posttranslational modifications. This may explain the distinct clinical phenotypes that are seen in patients with antibodies to antigens that are expressed throughout the brain. Furthermore, it is likely that there is a heterogeneous antibody population, consisting of different IgG subtypes and directed at multiple epitopes located in an immunogenic region. Binding of these antibodies may result in different pathophysiological mechanisms occurring in the same patient, together contributing to the clinical syndrome. Unraveling the predominant mechanism in each distinct antigen could provide clues for therapeutic interventions.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
تدمد: 1568-9972
العلاقة: https://dspace.library.uu.nl/handle/1874/307271Test
الإتاحة: https://dspace.library.uu.nl/handle/1874/307271Test
حقوق: info:eu-repo/semantics/EmbargoedAccess
رقم الانضمام: edsbas.8259165C
قاعدة البيانات: BASE