Immunomodulation by memantine in therapy of Alzheimer's disease is mediated through inhibition of Kv1.3 channels and T cell responsiveness.

2.50
Hdl Handle:
http://hdl.handle.net/10033/620568
Title:
Immunomodulation by memantine in therapy of Alzheimer's disease is mediated through inhibition of Kv1.3 channels and T cell responsiveness.
Authors:
Lowinus, Theresa; Bose, Tanima; Busse, Stefan; Busse, Mandy; Reinhold, Dirk; Schraven, Burkhart; Bommhardt, Ursula H H
Abstract:
Memantine is approved for the treatment of advanced Alzheimer´s disease (AD) and reduces glutamate-mediated neuronal excitotoxicity by antagonism of N-methyl-D-aspartate receptors. In the pathophysiology of AD immune responses deviate and infectious side effects are observed during memantine therapy. However, the particular effects of memantine on human T lymphocytes are unresolved. Here, we provide evidence that memantine blocks Kv1.3 potassium channels, inhibits CD3-antibody- and alloantigen-induced proliferation and suppresses chemokine-induced migration of peripheral blood T cells of healthy donors. Concurrent with the in vitro data, CD4+ T cells from AD patients receiving therapeutic doses of memantine show a transient decline of Kv1.3 channel activity and a long-lasting reduced proliferative response to alloantigens in mixed lymphocyte reactions. Furthermore, memantine treatment provokes a profound depletion of peripheral blood memory CD45RO+ CD4+ T cells. Thus, standard doses of memantine profoundly reduce T cell responses in treated patients through blockade of Kv1.3 channels. This may normalize deviant immunopathology in AD and contribute to the beneficial effects of memantine, but may also account for the enhanced infection rate.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Immunomodulation by memantine in therapy of Alzheimer's disease is mediated through inhibition of Kv1.3 channels and T cell responsiveness. 2016 Oncotarget
Journal:
Oncotarget
Issue Date:
22-Jul-2016
URI:
http://hdl.handle.net/10033/620568
DOI:
10.18632/oncotarget.10777
PubMed ID:
27462773
Type:
Article
ISSN:
1949-2553
Appears in Collections:
publications of the department of immune control (IMMK)

Full metadata record

DC FieldValue Language
dc.contributor.authorLowinus, Theresaen
dc.contributor.authorBose, Tanimaen
dc.contributor.authorBusse, Stefanen
dc.contributor.authorBusse, Mandyen
dc.contributor.authorReinhold, Dirken
dc.contributor.authorSchraven, Burkharten
dc.contributor.authorBommhardt, Ursula H Hen
dc.date.accessioned2016-11-04T10:28:09Z-
dc.date.available2016-11-04T10:28:09Z-
dc.date.issued2016-07-22-
dc.identifier.citationImmunomodulation by memantine in therapy of Alzheimer's disease is mediated through inhibition of Kv1.3 channels and T cell responsiveness. 2016 Oncotargeten
dc.identifier.issn1949-2553-
dc.identifier.pmid27462773-
dc.identifier.doi10.18632/oncotarget.10777-
dc.identifier.urihttp://hdl.handle.net/10033/620568-
dc.description.abstractMemantine is approved for the treatment of advanced Alzheimer´s disease (AD) and reduces glutamate-mediated neuronal excitotoxicity by antagonism of N-methyl-D-aspartate receptors. In the pathophysiology of AD immune responses deviate and infectious side effects are observed during memantine therapy. However, the particular effects of memantine on human T lymphocytes are unresolved. Here, we provide evidence that memantine blocks Kv1.3 potassium channels, inhibits CD3-antibody- and alloantigen-induced proliferation and suppresses chemokine-induced migration of peripheral blood T cells of healthy donors. Concurrent with the in vitro data, CD4+ T cells from AD patients receiving therapeutic doses of memantine show a transient decline of Kv1.3 channel activity and a long-lasting reduced proliferative response to alloantigens in mixed lymphocyte reactions. Furthermore, memantine treatment provokes a profound depletion of peripheral blood memory CD45RO+ CD4+ T cells. Thus, standard doses of memantine profoundly reduce T cell responses in treated patients through blockade of Kv1.3 channels. This may normalize deviant immunopathology in AD and contribute to the beneficial effects of memantine, but may also account for the enhanced infection rate.en
dc.languageENG-
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleImmunomodulation by memantine in therapy of Alzheimer's disease is mediated through inhibition of Kv1.3 channels and T cell responsiveness.
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalOncotargeten
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