{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:58:14Z","timestamp":1792133894582,"version":"4.4.0"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T00:00:00Z","timestamp":1669161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["303051\/2021\u20103"],"award-info":[{"award-number":["303051\/2021\u20103"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E\u201026\/202.667\/2019"],"award-info":[{"award-number":["E\u201026\/202.667\/2019"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Leprosy is a chronic infectious disease caused by <jats:italic>Mycobacterium leprae<\/jats:italic> infection in Schwann cells. Axonopathy is considered a hallmark of leprosy neuropathy and is associated with the irreversible motor and sensory loss seen in infected patients. Although <jats:italic>M. leprae<\/jats:italic> is recognized to provoke Schwann cell dedifferentiation, the mechanisms involved in the contribution of this phenomenon to neural damage remain unclear. In the present work, we used live <jats:italic>M. leprae<\/jats:italic> to infect the immortalized human Schwann cell line ST8814. The neurotoxicity of infected Schwann cell\u2010conditioned medium (SCCM) was then evaluated in a human neuroblastoma cell lineage and mouse neurons. ST8814 Schwann cells exposed to <jats:italic>M. leprae<\/jats:italic> affected neuronal viability by deviating glial <jats:sup>14<\/jats:sup>C\u2010labeled lactate, important fuel of neuronal central metabolism, to de novo lipid synthesis. The phenolic glycolipid\u20101 (PGL\u20101) is a specific <jats:italic>M. leprae<\/jats:italic> cell wall antigen proposed to mediate bacterial\u2013Schwann cell interaction. Therefore, we assessed the role of the PGL\u20101 on Schwann cell phenotype by using transgenic <jats:italic>M. bovis<\/jats:italic> (BCG)\u2010expressing the <jats:italic>M. leprae<\/jats:italic> PGL\u20101. We observed that BCG\u2010PGL\u20101 was able to induce a phenotype similar to <jats:italic>M. leprae<\/jats:italic>, unlike the wild\u2010type BCG strain. We next demonstrated that this Schwann cell neurotoxic phenotype, induced by <jats:italic>M. leprae<\/jats:italic> PGL\u20101, occurs through the protein kinase B (Akt) pathway. Interestingly, the pharmacological inhibition of Akt by triciribine significantly reduced free fatty acid content in the SCCM from <jats:italic>M. leprae\u2010<\/jats:italic> and BCG\u2010PGL\u20101\u2010infected Schwann cells and, hence, preventing neuronal death. Overall, these findings provide novel evidence that both <jats:italic>M. leprae<\/jats:italic> and PGL\u20101, induce a toxic Schwann cell phenotype, by modifying the host lipid metabolism, resulting in profound implications for neuronal loss. We consider this metabolic rewiring a new molecular mechanism to be the basis of leprosy neuropathy.<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15722-fig-0005-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1111\/jnc.15722","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T08:07:39Z","timestamp":1667981259000},"page":"158-171","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Phenolic glycolipid\u20101 of <i>Mycobacterium leprae<\/i> is involved in human Schwann cell line <scp>ST8814<\/scp> neurotoxic phenotype"],"prefix":"10.1111","volume":"164","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3099-4782","authenticated-orcid":false,"given":"Karina do Carmo de Vasconcelos","family":"Girardi","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Microbiologia Celular Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz  Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4172-2670","authenticated-orcid":false,"given":"Bruno Siqueira","family":"Mietto","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biol\u00f3gicas Universidade Federal de Juiz de Fora  Juiz de Fora Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9453-7241","authenticated-orcid":false,"given":"Karoline","family":"dos Anjos Lima","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica de Lip\u00eddeos e Lipoprote\u00ednas Instituto 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