流行病学研究表明帕金森病 (PD) 和恶性黑色素瘤之间存在巧合。有人认为这种关系至少部分归因于 α-突触核蛋白 (αSyn/Snca) 的调节。 αSyn 寡聚物在 PD 中积聚，引发典型的 PD 症状，在恶性黑色素瘤中积聚，增加肿瘤细胞的增殖。此外，αSyn 还会导致 PD 的非运动症状，包括疼痛。在这项研究中，我们利用全身和局部消耗 αSyn 的方法，在小鼠模型中研究了 αSyn 在黑色素瘤生长和黑色素瘤引起的疼痛中的作用。将 B16BL6 野生型和 αSyn 敲低黑色素瘤细胞分别接种到 αSyn 敲除小鼠和野生型小鼠的爪子中。在 21 天的时间内评估肿瘤生长和肿瘤引起的疼痛超敏反应。通过 RT-PCR 和 Western Blot 分析肿瘤、脊髓和坐骨神经的分子机制。我们的结果表明，Snca 的整体和局部消融都有助于减少肿瘤生长和减少肿瘤引起的机械异常性疼痛，尽管导致这些作用的机制不同。虽然在 Snca 敲除小鼠中注射野生型细胞会强烈增加肿瘤中的免疫反应，但局部 Snca 敲低会降低肿瘤中的自噬机制和炎症反应。总之，敲低 αSyn 可能是抑制黑色素瘤进展和减少肿瘤引起的疼痛的一种有前景的方法。© 2023 作者。 FASEB 期刊由 Wiley periodicals LLC 代表美国实验生物学学会联合会出版。

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-Synuclein (αSyn/Snca). αSyn oligomers accumulate in PD, which triggers typical PD symptoms, and in malignant melanoma, which increases the proliferation of tumor cells. In addition, αSyn contributes to non-motor symptoms of PD, including pain. In this study, we investigated the role of αSyn in melanoma growth and melanoma-induced pain in a mouse model using systemic and local depletion of αSyn. B16BL6 wild-type as well as αSyn knock-down melanoma cells were inoculated into the paws of αSyn knock-out mice and wild-type mice, respectively. Tumor growth and tumor-induced pain hypersensitivity were assessed over a period of 21 days. Molecular mechanisms were analyzed by RT-PCR 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-induced mechanical allodynia, though mechanisms contributing to these effects differ. While injection of wild-type cells in Snca knock-out mice strongly increased the immune response in the tumor, local Snca knock-down decreased autophagy mechanisms and the inflammatory reaction in the tumor. In conclusion, a knockdown of αSyn might constitute a promising approach to inhibiting the progression of melanoma and reducing tumor-induced pain.© 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.