Immunomodulation by memantine in therapy of Alzheimer's disease is mediated through inhibition of Kv1.3 channels and T cell responsiveness
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
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.