Cellular and Molecular Neurobiology<\/p>\n
Author:<\/strong> MARIANA IN\u00c9S HOLUBIEC LOJO | Email:<\/strong> mholubiec@fmed.uba.ar<\/p>\n Mariana In\u00e9s Holubiec 1\u00b0<\/sup>, Julieta Bianchelli 2\u00b0<\/sup>, Cayetana Arnaiz 2\u00b0<\/sup>, Melina Gonzalez Prinz 2\u00b0<\/sup>, Tomas Falzone 2\u00b0<\/sup><\/p>\n 1\u00b0 Instituto de Biolog\u00eda Celular y Neurociencia IBCN (UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, CABA, 1121, Buenos Aires, Argentina. Reactive Oxygen Species (ROS) and mitochondrial dysfunction are implicated in Alzheimer’s disease (AD). However, the exact mechanism involved remain unclear. Damage to mitochondrial membrane and inhibition of mitochondrial respiration are thought to contribute to the progression of the disease. However, the lack of suitable human models that replicate pathological features, together with impaired cellular pathways, constitutes a major challenge in AD studies. We induced pluripotency in patient-derived skin fibroblasts carrying the Swedish mutation in App (APPswe), to generate human brain organoids that model AD, and Author: HOLUBIEC LOJO MARIANA IN\u00c9S | email: mholubiec@fmed.uba.ar | Cellular and Molecular Neurobiology<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[34],"tags":[18],"class_list":["post-1892","post","type-post","status-publish","format-standard","hentry","category-session-2","tag-cellular-and-molecular-neurobiology"],"_links":{"self":[{"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/posts\/1892","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/comments?post=1892"}],"version-history":[{"count":2,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/posts\/1892\/revisions"}],"predecessor-version":[{"id":2418,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/posts\/1892\/revisions\/2418"}],"wp:attachment":[{"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/media?parent=1892"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/categories?post=1892"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/tags?post=1892"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
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\n2\u00b0 Instituto de Investigaci\u00f3n en Biomedicina de Buenos Aires IBioBA (MPSP-CONICET), Partner Institute of the Max Planck Society, Godoy Cruz 2390, CABA, 1425, Buenos Aires, Argentina.<\/p>\n
\nstudied redox regulation and mitochondrial homeostasis. We found AD-related pathological hallmarks in APPswe organoids, including elevated A? levels, increased extracellular amyloid deposits, and enhanced tau phosphorylation. Using live-imaging spinning-disk confocal microscopy, we found an increase in mitochondrial fragmentation and a significant loss of mitochondrial membrane potential in APPswe brain organoids subjected to oxidative conditions. Ratiometric dyes revealed a selective increase in mitochondrial superoxide anion and hydrogen peroxide levels in APPswe organoids, coupled to impairments in cytosolic and mitochondrial redoxin expression. This suggests a selective increase in mitochondrial vulnerability to oxidative conditions in APPswe organoids, indicating that the abnormal metabolism of APP leads to specific changes in mitochondrial homeostasis.<\/p>\n","protected":false},"excerpt":{"rendered":"