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@ARTICLE{Hose:302827,
      author       = {M. Hose and A. Ninnemann and H. Abberger and F. Schumacher
                      and E. Naser and L. Purkart and F. Korbmacher and L. Martins
                      Nascentes Melo$^*$ and N. Beckmann and V. Blietschau and J.
                      Falkenstein and B. Kleuser and A. Tasdogan and E. Gulbins
                      and A. Carpinteiro and R. Klopfleisch and J. Buer and A. M.
                      Westendorf and K. Matuschewski and W. Hansen},
      title        = {{A}mitriptyline inhibits {P}lasmodium development in
                      infected red blood cells by modulating sphingolipid
                      metabolism and glucose uptake.},
      journal      = {Biomedicine $\&$ pharmacotherapy},
      volume       = {189},
      issn         = {0753-3322},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2025-01367},
      pages        = {118331},
      year         = {2025},
      abstract     = {Malaria remains a global health challenge, necessitating
                      novel therapeutic approaches. Here, we explore the role of
                      the sphingolipid metabolism in Plasmodium infection. We
                      focus on the enzyme acid sphingomyelinase (Asm), which
                      hydrolyzes sphingomyelin to ceramide, a structural but also
                      bioactive membrane molecule. We demonstrate induction of Asm
                      activity in infected mice, leading to elevated ceramide
                      levels in infected red blood cells. Pharmacological
                      inhibition of Asm with the functional inhibitor
                      amitriptyline in Plasmodium yoelii (Py)- and Plasmodium
                      berghei ANKA (PbA)-infected mice significantly reduces
                      parasitemia and mitigates disease-associated pathology.
                      Amitriptyline treatment also reduces T cell activation,
                      preserving blood-brain barrier integrity upon PbA infection.
                      Remarkably, we observe inhibition of Plasmodium falciparum
                      growth in vitro upon exposure to amitriptyline.
                      Mechanistically, we elucidate that amitriptyline impedes
                      intra-erythrocytic parasite development, due to a reduced
                      glucose uptake and thereby interfering with the spreading of
                      blood-stage Plasmodium parasites. Our findings highlight the
                      therapeutic promise of targeting sphingolipid metabolism to
                      combat Plasmodium infections.},
      keywords     = {Acid sphingomyelinase (Other) / Amitriptyline (Other) /
                      Ceramide (Other) / Glucose (Other) / Malaria (Other) / S1P
                      (Other)},
      cin          = {ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40633203},
      doi          = {10.1016/j.biopha.2025.118331},
      url          = {https://inrepo02.dkfz.de/record/302827},
}