{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:23:28Z","timestamp":1790832208180,"version":"4.1.0"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2017,7,1]],"date-time":"2017-07-01T00:00:00Z","timestamp":1498867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Mutations in the Presenilin genes are the major genetic cause of Alzheimer\u2019s disease. Presenilin and Nicastrin are essential components of \u03b3-secretase, a multi-subunit protease that cleaves Type I transmembrane proteins. Genetic studies in mice previously demonstrated that conditional inactivation of Presenilin or Nicastrin in excitatory neurons of the postnatal forebrain results in memory deficits, synaptic impairment, and age-dependent neurodegeneration. The roles of Drosophila Presenilin (Psn) and Nicastrin (Nct) in the adult fly brain, however, are unknown. To knockdown (KD) Psn or Nct selectively in neurons of the adult brain, we generated multiple shRNA lines. Using a ubiquitous driver, these shRNA lines resulted in 80\u201390% reduction of mRNA and pupal lethality\u2014a phenotype that is shared with Psn and Nct mutants carrying nonsense mutations. Furthermore, expression of these shRNAs in the wing disc caused notching wing phenotypes, which are also shared with Psn and Nct mutants. Similar to Nct, neuron-specific Psn KD using two independent shRNA lines led to early mortality and rough eye phenotypes, which were rescued by a fly Psn transgene. Interestingly, conditional KD (cKD) of Psn or Nct in adult neurons using the elav-Gal4 and tubulin-Gal80ts system caused shortened lifespan, climbing defects, increases in apoptosis, and age-dependent neurodegeneration. Together, these findings demonstrate that, similar to their mammalian counterparts, Drosophila Psn and Nct are required for neuronal survival during aging and normal lifespan, highlighting an evolutionarily conserved role of Presenilin in neuronal protection in the aging brain.<\/jats:p>","DOI":"10.1534\/genetics.116.196881","type":"journal-article","created":{"date-parts":[[2017,5,12]],"date-time":"2017-05-12T01:10:44Z","timestamp":1494551444000},"page":"1479-1493","source":"Crossref","is-referenced-by-count":26,"title":["An Evolutionarily Conserved Role of Presenilin in Neuronal Protection in the Aging <i>Drosophila<\/i> Brain"],"prefix":"10.1093","volume":"206","author":[{"given":"Jongkyun","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Neurology , Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Neurology , Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Perrimon","sequence":"additional","affiliation":[{"name":"Department of Genetics , Harvard Medical School, Boston, Massachusetts 02115"},{"name":"Howard Hughes Medical Institute , Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Neurology , Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts 02115"},{"name":"Program in Neuroscience , Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,7,1]]},"reference":[{"key":"2022110312580719400_bib1","doi-asserted-by":"crossref","first-page":"e234","DOI":"10.1371\/journal.pgen.0030234","article-title":"dAtaxin-2 mediates expanded Ataxin-1-induced neurodegeneration in a Drosophila model of SCA1.","volume":"3","author":"Al-Ramahi","year":"2007","journal-title":"PLoS Genet."},{"key":"2022110312580719400_bib2","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/nature14892","article-title":"An atomic structure of human gamma-secretase.","volume":"525","author":"Bai","year":"2015","journal-title":"Nature"},{"key":"2022110312580719400_bib3","doi-asserted-by":"crossref","first-page":"46907","DOI":"10.1074\/jbc.M409544200","article-title":"Reduced \u03b2-amyloid production and increased inflammatory responses in presenilin conditional knock-out mice.","volume":"279","author":"Beglopoulos","year":"2004","journal-title":"J. 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