Neuronal Rubicon Represses Extracellular APP/Amyloid β Deposition in Alzheimer’s Disease

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dc.contributor.authorEspinoza, Sandra
dc.contributor.authorGrunenwald, Felipe
dc.contributor.authorGomez, Wileidy
dc.contributor.authorGarcía, Felipe
dc.contributor.authorAbarzúa, Lorena
dc.contributor.authorOyarce, Sebastián
dc.contributor.authorHernández, María
dc.contributor.authorCortés, Bastián
dc.contributor.authorUhrig, Markus
dc.contributor.authorPonce, Daniela
dc.contributor.authorDurán, Claudia
dc.contributor.authorHetz, Claudio
dc.contributor.authorSanMartín, Carol
dc.contributor.authorCornejo, Victor
dc.contributor.authorEzquer, Fernando
dc.contributor.authorParra, Valentina
dc.contributor.authorBehrens, María
dc.contributor.authorManque, Patricio
dc.contributor.authorRojas, Diego
dc.contributor.authorVidal, René
dc.contributor.authorWoehlbier, Ute
dc.contributor.authorNassif, Melissa
dc.date.accessioned2022-11-14T19:02:34Z
dc.date.available2022-11-14T19:02:34Z
dc.date.issued2022
dc.description.abstractAlzheimer’s disease (AD) is the most prevalent age-associated neurodegenerative disease. A decrease in autophagy during aging contributes to brain disorders by accumulating potentially toxic substrates in neurons. Rubicon is a well-established inhibitor of autophagy in all cells. However, Rubicon participates in different pathways depending on cell type, and little information is currently available on neuronal Rubicon’s role in the AD context. Here, we investigated the cell-specific expression of Rubicon in postmortem brain samples from AD patients and 5xFAD mice and its impact on amyloid β burden in vivo and neuroblastoma cells. Further, we assessed Rubicon levels in human-induced pluripotent stem cells (hiPSCs), derived from early-to-moderate AD and in postmortem samples from severe AD patients. We found increased Rubicon levels in AD-hiPSCs and postmortem samples and a notable Rubicon localization in neurons. In AD transgenic mice lacking Rubicon, we observed intensified amyloid β burden in the hippocampus and decreased Pacer and p62 levels. In APP-expressing neuroblastoma cells, increased APP/amyloid β secretion in the medium was found when Rubicon was absent, which was not observed in cells depleted of Atg5, essential for autophagy, or Rab27a, required for exosome secretion. Our results propose an uncharacterized role of Rubicon on APP/amyloid β homeostasis, in which neuronal Rubicon is a repressor of APP/amyloid β secretion, defining a new way to target AD and other similar diseases therapeuticallyes
dc.description.versionVersión publicadaes
dc.identifier.citationEspinoza, S.; Grunenwald, F.; Gomez, W.; García, F.; Abarzúa-Catalan, L.; Oyarce-Pezoa, S.; Hernandez, M.F.; Cortés, B.I.; Uhrig, M.; Ponce, D.P.; et al. Neuronal Rubicon Represses Extracellular APP/Amyloid β Deposition in Alzheimer’s Disease. Cells 2022, 11, 1860. https:// doi.org/10.3390/cells11121860es
dc.identifier.urihttps://doi.org/10.3390/cells11121860es
dc.identifier.urihttp://hdl.handle.net/11447/6657
dc.language.isoenes
dc.subjectAlzheimer’s diseasees
dc.subjectAutophagyes
dc.subjectRubicones
dc.subjectKIAA0226es
dc.subjectRUBCNes
dc.subjectAPPes
dc.subjectKIAA0226Les
dc.subjectPaceres
dc.titleNeuronal Rubicon Represses Extracellular APP/Amyloid β Deposition in Alzheimer’s Diseasees
dc.typeArticlees
dcterms.sourceCellses

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