--- res: bibo_abstract: - Optogenetics has been harnessed to shed new mechanistic light on current and future therapeutic strategies. This has been to date achieved by the regulation of ion flow and electrical signals in neuronal cells and neural circuits that are known to be affected by disease. In contrast, the optogenetic delivery of trophic biochemical signals, which support cell survival and are implicated in degenerative disorders, has never been demonstrated in an animal model of disease. Here, we reengineered the human and Drosophila melanogaster REarranged during Transfection (hRET and dRET) receptors to be activated by light, creating one-component optogenetic tools termed Opto-hRET and Opto-dRET. Upon blue light stimulation, these receptors robustly induced the MAPK/ERK proliferative signaling pathway in cultured cells. In PINK1B9 flies that exhibit loss of PTEN-induced putative kinase 1 (PINK1), a kinase associated with familial Parkinson’s disease (PD), light activation of Opto-dRET suppressed mitochondrial defects, tissue degeneration and behavioral deficits. In human cells with PINK1 loss-of-function, mitochondrial fragmentation was rescued using Opto-dRET via the PI3K/NF-кB pathway. Our results demonstrate that a light-activated receptor can ameliorate disease hallmarks in a genetic model of PD. The optogenetic delivery of trophic signals is cell type-specific and reversible and thus has the potential to inspire novel strategies towards a spatio-temporal regulation of tissue repair.@eng bibo_authorlist: - foaf_Person: foaf_givenName: Álvaro foaf_name: Inglés Prieto, Álvaro foaf_surname: Inglés Prieto foaf_workInfoHomepage: http://www.librecat.org/personId=2A9DB292-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0002-5409-8571 - foaf_Person: foaf_givenName: Nikolas foaf_name: Furthmann, Nikolas foaf_surname: Furthmann - foaf_Person: foaf_givenName: Samuel H. foaf_name: Crossman, Samuel H. foaf_surname: Crossman - foaf_Person: foaf_givenName: Alexandra Madelaine foaf_name: Tichy, Alexandra Madelaine foaf_surname: Tichy - foaf_Person: foaf_givenName: Nina foaf_name: Hoyer, Nina foaf_surname: Hoyer - foaf_Person: foaf_givenName: Meike foaf_name: Petersen, Meike foaf_surname: Petersen - foaf_Person: foaf_givenName: Vanessa foaf_name: Zheden, Vanessa foaf_surname: Zheden foaf_workInfoHomepage: http://www.librecat.org/personId=39C5A68A-F248-11E8-B48F-1D18A9856A87 - foaf_Person: foaf_givenName: Julia foaf_name: Bicher, Julia foaf_surname: Bicher foaf_workInfoHomepage: http://www.librecat.org/personId=3CCBB46E-F248-11E8-B48F-1D18A9856A87 - foaf_Person: foaf_givenName: Eva foaf_name: Gschaider-Reichhart, Eva foaf_surname: Gschaider-Reichhart foaf_workInfoHomepage: http://www.librecat.org/personId=3FEE232A-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0002-7218-7738 - foaf_Person: foaf_givenName: Attila foaf_name: György, Attila foaf_surname: György foaf_workInfoHomepage: http://www.librecat.org/personId=3BCEDBE0-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0002-1819-198X - foaf_Person: foaf_givenName: Daria E foaf_name: Siekhaus, Daria E foaf_surname: Siekhaus foaf_workInfoHomepage: http://www.librecat.org/personId=3D224B9E-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0001-8323-8353 - foaf_Person: foaf_givenName: Peter foaf_name: Soba, Peter foaf_surname: Soba - foaf_Person: foaf_givenName: Konstanze F. foaf_name: Winklhofer, Konstanze F. foaf_surname: Winklhofer - foaf_Person: foaf_givenName: Harald L foaf_name: Janovjak, Harald L foaf_surname: Janovjak foaf_workInfoHomepage: http://www.librecat.org/personId=33BA6C30-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0002-8023-9315 bibo_doi: 10.1371/journal.pgen.1009479 bibo_issue: '4' bibo_volume: 17 dct_date: 2021^xs_gYear dct_identifier: - UT:000640606700001 dct_isPartOf: - http://id.crossref.org/issn/15537404 dct_language: eng dct_publisher: Public Library of Science@ dct_title: Optogenetic delivery of trophic signals in a genetic model of Parkinson's disease@ ...