{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:02:39Z","timestamp":1781107359202,"version":"3.54.1"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"26","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">PIK3CA<\/jats:italic>\n                    -related disorders are rare genetic disorders due to somatic gain-of-function mutations in\n                    <jats:italic toggle=\"yes\">PIK3CA<\/jats:italic>\n                    during embryonic development, a pathway involved in cell growth, proliferation, and metabolism. Accumulating evidence from patients with\n                    <jats:italic toggle=\"yes\">PIK3CA<\/jats:italic>\n                    -related disorders indicates that peripheral nerves are frequently affected, leading to severe neurological symptoms. However, the exact underlying mechanism of these disorders remains unclear. To address this, we developed a mouse model with a\n                    <jats:italic toggle=\"yes\">PIK3CA<\/jats:italic>\n                    gain-of-function mutation specifically in Schwann cells, which successfully mirrored the clinical features observed in patients. In this model, we observed that\n                    <jats:italic toggle=\"yes\">PIK3CA<\/jats:italic>\n                    -mutated cells communicate with neighboring healthy cells, such as adipocytes and hair follicles, through a unique crosstalk mechanism that triggers their growth, proliferation, and anagen phase expansion. Additionally, we demonstrated that\n                    <jats:italic toggle=\"yes\">PIK3CA<\/jats:italic>\n                    mutation in peripheral nerves leads to a metabolic shift through glycolytic activation. We investigated the effects of alpelisib, an approved pharmacological inhibitor of PIK3CA, in the model. Early administration of alpelisib significantly improved the signs and symptoms in the mice. However, when treatment was delayed, its efficacy was diminished due to the drug\u2019s inability to penetrate the myelin sheath effectively. In summary, our study offers a valuable mouse model for studying\n                    <jats:italic toggle=\"yes\">PIK3CA<\/jats:italic>\n                    -related neuropathy, uncovers a unique communication between healthy and affected tissues, and highlights the potential benefits of early pharmacological intervention using alpelisib.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2424867122","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T11:37:29Z","timestamp":1750765049000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":5,"title":["<i>PIK3CA<\/i>\n                    gain-of-function mutation in Schwann cells leads to severe neuropathy and aerobic glycolysis through a non-cell autonomous effect"],"prefix":"10.1073","volume":"122","author":[{"given":"Quitterie","family":"Venot","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9","place":["Paris, France"]},{"name":"INSERM U1151, Institut Necker-Enfants Malades","place":["Paris, France"]},{"name":"Unit\u00e9 de M\u00e9decine Translationnelle et Th\u00e9rapies Cibl\u00e9es, H\u00f4pital Necker-Enfants Malades, Assistance Publique H\u00f4pitaux de Paris","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5239-1596","authenticated-orcid":false,"given":"Marina","family":"Firpion","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9","place":["Paris, France"]},{"name":"INSERM U1151, Institut Necker-Enfants Malades","place":["Paris, France"]},{"name":"Unit\u00e9 de M\u00e9decine Translationnelle et Th\u00e9rapies Cibl\u00e9es, H\u00f4pital Necker-Enfants Malades, Assistance Publique H\u00f4pitaux de Paris","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Ladraa","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris 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