{"id":1317,"date":"2023-09-26T15:01:42","date_gmt":"2023-09-26T18:01:42","guid":{"rendered":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/2023\/09\/26\/181-engineered-tau-micrornas-modulate-neuronal-physiology-and-rescue-tauopathy-phenotypes-in-a-preclinical-model\/"},"modified":"2023-09-26T20:36:45","modified_gmt":"2023-09-26T23:36:45","slug":"181-engineered-tau-micrornas-modulate-neuronal-physiology-and-rescue-tauopathy-phenotypes-in-a-preclinical-model","status":"publish","type":"post","link":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/2023\/09\/26\/181-engineered-tau-micrornas-modulate-neuronal-physiology-and-rescue-tauopathy-phenotypes-in-a-preclinical-model\/","title":{"rendered":"181 | Engineered Tau microRNAs modulate neuronal physiology and rescue tauopathy phenotypes in a preclinical model"},"content":{"rendered":"<p>Disorders of the Nervous System<\/p>\n<p><strong>Author:<\/strong> Carolina Luc\u00eda Facal | <strong>Email:<\/strong> carolinaluciafacal@gmail.com<\/p>\n<hr>\n<p>Carolina Luc\u00eda Facal <sup>1\u00b0<\/sup>, Iv\u00e1n Fern\u00e1ndez-Bessone <sup>2\u00b0<\/sup>, Javier Andr\u00e9s Mu\u00f1iz <sup>1\u00b0<\/sup>, A. Ezequiel Pereyra <sup>1\u00b0<\/sup>, Olivia Pedroncini <sup>3\u00b0<\/sup>, Cayetana Arnaiz <sup>3\u00b0<\/sup>, Ramiro Clerici-Delville <sup>1\u00b0<\/sup>, Indiana P\u00e1ez-Paz <sup>1\u00b0<\/sup>, Leandro Urrutia <sup>4\u00b0<\/sup>, Germ\u00e1n Falasco <sup>4\u00b0<\/sup><\/p>\n<p>1\u00b0 Instituto de Investigaciones en Ingenier\u00eda Gen\u00e9tica y Biolog\u00eda Molecular (INGEBI-CONICET)<br \/>\n2\u00b0 Instituto de Biolog\u00eda Celular y Neurociencias (IBCN-UBA-CONICET)<br \/>\n3\u00b0 Instituto de Investigaci\u00f3n en Biomedicina de Buenos Aires (IBioBA-CONICET-MPSP)<br \/>\n4\u00b0 Centro de Im\u00e1genes Moleculares (FLENI)<\/p>\n<p>Abnormal protein tau accumulation is the hallmark of several neurodegenerative diseases, named tauopathies. Strategies directed to reduce tau in the brain are promising for therapeutic intervention, yet, development of long-term treatments needs optimization, and better understating of the functional pathways potentially affected by tau reduction. Here we developed artificial microRNAs targeting the human MAPT mRNA to dwindle tau protein synthesis. In human differentiated neurons in culture, microRNAs-directed tau reduction decreased neuronal firing but did not affect neuronal morphology nor impaired axonal transport. In turn, in the htau mouse model of tauopathy, microRNA expression into the medial prefrontal cortex prevented pathological tau accumulation, modulated firing activity of putative pyramidal neurons, and improved glucose uptake in PET scans. Moreover, local tau knockdown prevented cognitive decline in aged htau mice. Our results demonstrate target engagement of designed tau-microRNAs and provide proof of concept for their therapeutic benefit to rescue tauopathy-related phenotypes.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Author: Facal Carolina Luc\u00eda | email: carolinaluciafacal@gmail.com | Disorders of the Nervous System<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[17],"tags":[22],"class_list":["post-1317","post","type-post","status-publish","format-standard","hentry","category-session-1","tag-disorders-of-the-nervous-system"],"_links":{"self":[{"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/posts\/1317","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=1317"}],"version-history":[{"count":3,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/posts\/1317\/revisions"}],"predecessor-version":[{"id":1802,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/posts\/1317\/revisions\/1802"}],"wp:attachment":[{"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/media?parent=1317"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/categories?post=1317"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/tags?post=1317"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}