Research Papers:

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

Theresa Lowinus, Tanima Bose, Stefan Busse, Mandy Busse, Dirk Reinhold, Burkhart Schraven and Ursula H.H. Bommhardt _

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2016; 7:53797-53807. https://doi.org/10.18632/oncotarget.10777

Metrics: PDF 1533 views  |   HTML 1372 views  |   ?  


Theresa Lowinus1, Tanima Bose2,6, Stefan Busse3, Mandy Busse4, Dirk Reinhold1, Burkhart Schraven1,5, Ursula H.H. Bommhardt1

1Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany

2Molecular Physiology, Leibniz Institute for Neurobiology, Magdeburg, Germany

3Department of Psychiatry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany

4Department of Pediatric Pulmonology & Allergology, Medical University of Hannover, Hannover, Germany

5Department of Immune Control, Helmholtz Centre for Infection Research, Braunschweig, Germany

6Current address: Lee Kong Chian School of Medicine, Singapore

Correspondence to:

Ursula H.H. Bommhardt, email: Ursula.Bommhardt@med.ovgu.de

Keywords: human T cells, memantine, Kv1.3 potassium channel, NMDA receptor antagonist, Alzheimer´s disease

Received: February 04, 2016    Accepted: July 09, 2016    Published: July 22, 2016


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.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 10777