Neurochemistry and Neuropharmacology<\/p>\n
Author:<\/strong> Mar\u00eda del Milagro Teran | Email:<\/strong> maria0191@hotmail.com<\/p>\n Mar\u00eda del Milagro Teran 1\u00b0<\/sup>, Rodrigo Tomas Grau 1\u00b0<\/sup>, Estefan\u00eda Sol\u00edz Santander 1\u00b0<\/sup>, \u00c1lvaro Luna Mercado 1\u00b0<\/sup>, C\u00e9sar \u00c1vila 1\u00b0<\/sup>, Rita Raisman-Vozari 2\u00b0<\/sup>, Bruno Figadere 3\u00b0<\/sup>, Diego Ploper 1\u00b0<\/sup>, Rosana Cheh\u00edn 1\u00b0<\/sup><\/p>\n 1\u00b0 Instituto de Investigaci\u00f3n en Medicina Molecular y Celular Aplicada (IMMCA) (CONICET-UNT-SIPROSA) Parkinson’s disease (PD) is a chronic neurodegenerative disorder characterized by the loss of dopaminergic neurons due to misfolding and aggregation of a-synuclein (aS) protein. These toxic aggregates disrupt normal cellular processes, leading to neuronal dysfunction and death. Although previous reports indicate that doxycycline (DOX) has the potential to interfere with aS aggregation, its antibiotic activity confers a limitation for long-term treatments. Here, we synthesized and tested a novel reduced form of DOX (DDox), with diminished antibacterial activity. DDox exhibited an enhanced and dose-dependent anti-aggregating effect against aS. Additionally, DDox showed no toxicity in SH-SY5Y cell lines. Moreover, in transgenic SH-SY5Y-aS-RFP cells where endogenous aS aggregates were induced by treatment with exogenous pre-formed aS fibrils (aS PFF), co-treatment with DDox reduced ?S seeding. However, the same effect was not observed when DDox was used as a pre-treatment, suggesting a direct effect on aS PFF. Remarkably, DDox inhibited fluorescentlly-labeled aS PFF uptake and aS PFF-triggered lysosomal stress, which represent novel properties for tetracyclines in PD models. Our results suggest that DDox is a non-toxic molecule with non-antibiotic activity and neuroprotective properties, which make it attractive for in vivo preclinical PD studies.<\/p>\n","protected":false},"excerpt":{"rendered":" Author: Teran Mar\u00eda del Milagro | email: maria0191@hotmail.com | Neurochemistry and Neuropharmacology<\/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":[25],"class_list":["post-1998","post","type-post","status-publish","format-standard","hentry","category-session-2","tag-neurochemistry-and-neuropharmacology"],"_links":{"self":[{"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/posts\/1998","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=1998"}],"version-history":[{"count":1,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/posts\/1998\/revisions"}],"predecessor-version":[{"id":2167,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/posts\/1998\/revisions\/2167"}],"wp:attachment":[{"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/media?parent=1998"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/categories?post=1998"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/tags?post=1998"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
\n
\n2\u00b0 Paris Brain Institute-ICM, Inserm, CNRS, Sorbonne Universit\u00e9 APHP, H\u00f4pital de la Piti\u00e9 la Piti\u00e9-Salp\u00eatri\u00e8re
\n3\u00b0 BioCIS, Universit\u00e9 Paris-Saclay, CNRS<\/p>\n