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Unfortunately, few pharmacological options are available for NFII. Here, we undertake a genome-wide CRISPR\/Cas9 screen to search for synthetic-lethal genes that, when inhibited, cause death of NF2 mutant Schwann cells but not NF2 wildtype cells. We identify\n                    <jats:italic>ACSL3<\/jats:italic>\n                    and\n                    <jats:italic>G6PD<\/jats:italic>\n                    as two synthetic-lethal partners for\n                    <jats:italic>NF2<\/jats:italic>\n                    , both involved in lipid biogenesis and cellular redox. We find that\n                    <jats:italic>NF2<\/jats:italic>\n                    mutant Schwann cells are more oxidized than control cells, in part due to reduced expression of genes involved in NADPH generation such as\n                    <jats:italic>ME1<\/jats:italic>\n                    . Since G6PD and ME1 redundantly generate cytosolic NADPH, lack of either one is compatible with cell viability, but not down-regulation of both. Since genetic deficiency for\n                    <jats:italic>G6PD<\/jats:italic>\n                    is tolerated in the human population, G6PD could be a good pharmacological target for NFII.\n                  <\/jats:p>","DOI":"10.1038\/s41467-024-49298-7","type":"journal-article","created":{"date-parts":[[2024,6,15]],"date-time":"2024-06-15T03:03:06Z","timestamp":1718420586000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["G6PD and ACSL3 are synthetic lethal partners of NF2 in Schwann cells"],"prefix":"10.1038","volume":"15","author":[{"given":"Athena","family":"Kyrkou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Valla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5841-225X","authenticated-orcid":false,"given":"Yao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Ambrosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Laier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"M\u00fcller-Decker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Boutros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4237-9368","authenticated-orcid":false,"given":"Aurelio A.","family":"Teleman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,15]]},"reference":[{"key":"49298_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-4-16","volume":"4","author":"DG Evans","year":"2009","unstructured":"Evans, D. 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