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The exposure of PNS axons to extracellular TTR deposits leads to an axonopathy that culminates in neuronal death. However, the molecular mechanisms underlying TTR-induced neurodegeneration are still unclear, despite the extensive studies in vertebrate models. In this work we used a <jats:italic>Drosophila<\/jats:italic> FAP model, based on the expression of the amyloidogenic TTR (V30M) in the fly retina, to uncover genetic interactions with cytoskeleton regulators. We show that TTR interacts with actin regulators and induces cytoskeleton alterations, leading to axonal defects. Moreover, our study pinpoints an interaction between TTRV30M and members of Rho GTPase signaling pathways, the major actin regulators. Based on these findings we propose that actin cytoskeleton alterations may mediate the axonopathy observed in FAP patients, and highlight a molecular pathway, mediated by Rho GTPases, underlying TTR-induced neurodegeneration. We expect this work to prompt novel studies and approaches towards FAP therapy.<\/jats:p>","DOI":"10.1038\/s41598-020-70377-4","type":"journal-article","created":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T06:06:55Z","timestamp":1597212415000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Transthyretin interacts with actin regulators in a Drosophila model of familial amyloid polyneuropathy"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8941-5805","authenticated-orcid":false,"given":"Marina","family":"I. Oliveira da Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla S.","family":"Lopes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rcia A.","family":"Liz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,12]]},"reference":[{"key":"70377_CR1","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1093\/brain\/94.2.207","volume":"94","author":"A Coimbra","year":"1971","unstructured":"Coimbra, A. & Andrade, C. Familial amyloid polyneuropathy: an electron microscope study of the peripheral nerve in five cases. II. Nerve fibre changes. 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