{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T10:46:56Z","timestamp":1776682016702,"version":"3.51.2"},"reference-count":53,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T00:00:00Z","timestamp":1699228800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Epidemiological studies show a coincidence between Parkinson's disease (PD) and malignant melanoma. It has been suggested that this relationship is due, at least in part, to modulation of alpha\u2010Synuclein (\u03b1Syn\/Snca). \u03b1Syn oligomers accumulate in PD, which triggers typical PD symptoms, and in malignant melanoma, which increases the proliferation of tumor cells. In addition, \u03b1Syn contributes to non\u2010motor symptoms of PD, including pain. In this study, we investigated the role of \u03b1Syn in melanoma growth and melanoma\u2010induced pain in a mouse model using systemic and local depletion of \u03b1Syn. B16BL6 wild\u2010type as well as \u03b1Syn knock\u2010down melanoma cells were inoculated into the paws of \u03b1Syn knock\u2010out mice and wild\u2010type mice, respectively. Tumor growth and tumor\u2010induced pain hypersensitivity were assessed over a period of 21\u2009days. Molecular mechanisms were analyzed by RT\u2010PCR and Western Blot in tumors, spinal cord, and sciatic nerve. Our results indicate that both global and local ablation of Snca contribute to reduced tumor growth and to a reduction of tumor\u2010induced mechanical allodynia, though mechanisms contributing to these effects differ. While injection of wild\u2010type cells in Snca knock\u2010out mice strongly increased the immune response in the tumor, local Snca knock\u2010down decreased autophagy mechanisms and the inflammatory reaction in the tumor. In conclusion, a knockdown of \u03b1Syn might constitute a promising approach to inhibiting the progression of melanoma and reducing tumor\u2010induced pain.<\/jats:p>","DOI":"10.1096\/fj.202301489r","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T11:19:13Z","timestamp":1699269553000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Distinct molecular mechanisms contribute to the reduction of melanoma growth and tumor pain after systemic and local depletion of\n                    <scp>alpha\u2010Synuclein<\/scp>\n                    in mice"],"prefix":"10.1096","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3909-5751","authenticated-orcid":false,"given":"Ellen","family":"Niederberger","sequence":"first","affiliation":[{"name":"Goethe\u2010Universit\u00e4t Frankfurt, Universit\u00e4tsklinikum pharmazentrum frankfurt\/ZAFES, Institut f\u00fcr Klinische 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