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@ARTICLE{PrezSisqus:154788,
      author       = {Pérez-Sisqués, Leticia and Sancho-Balsells, Anna and
                      Solana-Balaguer, Júlia and Campoy-Campos, Genís and
                      Vives-Isern, Marcel and Soler-Palazón, Ferran and
                      Anglada-Huguet, Marta and López-Toledano, Miguel-Ángel and
                      Mandelkow, Eva-Maria and Alberch, Jordi and Giralt, Albert
                      and Malagelada, Cristina},
      title        = {{RTP}801/{REDD}1 contributes to neuroinflammation severity
                      and memory impairments in {A}lzheimer’s disease},
      journal      = {Cell death $\&$ disease},
      volume       = {12},
      number       = {6},
      issn         = {2041-4889},
      address      = {London [u.a.]},
      publisher    = {Nature Publishing Group},
      reportid     = {DZNE-2021-00368},
      pages        = {616},
      year         = {2021},
      abstract     = {RTP801/REDD1 is a stress-regulated protein whose
                      upregulation is necessary and sufficient to trigger neuronal
                      death. Its downregulation in Parkinson's and Huntington's
                      disease models ameliorates the pathological phenotypes. In
                      the context of Alzheimer's disease (AD), the coding gene for
                      RTP801, DDIT4, is responsive to Aβ and modulates its
                      cytotoxicity in vitro. Also, RTP801 mRNA levels are
                      increased in AD patients' lymphocytes. However, the
                      involvement of RTP801 in the pathophysiology of AD has not
                      been yet tested. Here, we demonstrate that RTP801 levels are
                      increased in postmortem hippocampal samples from AD
                      patients. Interestingly, RTP801 protein levels correlated
                      with both Braak and Thal stages of the disease and with GFAP
                      expression. RTP801 levels are also upregulated in
                      hippocampal synaptosomal fractions obtained from murine
                      5xFAD and rTg4510 mice models of the disease. A local RTP801
                      knockdown in the 5xFAD hippocampal neurons with
                      shRNA-containing AAV particles ameliorates cognitive
                      deficits in 7-month-old animals. Upon RTP801 silencing in
                      the 5xFAD mice, no major changes were detected in
                      hippocampal synaptic markers or spine density. Importantly,
                      we found an unanticipated recovery of several gliosis
                      hallmarks and inflammasome key proteins upon neuronal RTP801
                      downregulation in the 5xFAD mice. Altogether our results
                      suggest that RTP801 could be a potential future target for
                      theranostic studies since it could be a biomarker of
                      neuroinflammation and neurotoxicity severity of the disease
                      and, at the same time, a promising therapeutic target in the
                      treatment of AD.},
      keywords     = {Alzheimer Disease: complications / Alzheimer Disease:
                      genetics / Alzheimer Disease: pathology / Animals /
                      Case-Control Studies / Disease Models, Animal /
                      Encephalitis: etiology / Encephalitis: genetics /
                      Encephalitis: pathology / Female / Humans / Male / Memory
                      Disorders: etiology / Memory Disorders: genetics / Memory
                      Disorders: pathology / Mice / Mice, Transgenic /
                      Neuroimmunomodulation: genetics / Neurotoxicity Syndromes:
                      etiology / Neurotoxicity Syndromes: genetics / Neurotoxicity
                      Syndromes: pathology / Severity of Illness Index /
                      Transcription Factors: physiology},
      cin          = {AG Mandelkow 2},
      ddc          = {570},
      cid          = {I:(DE-2719)1013015},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34131105},
      pubmed       = {34131105},
      pmc          = {pmc:PMC8206344},
      doi          = {10.1038/s41419-021-03899-y},
      url          = {https://pub.dzne.de/record/154788},
}