| First Author | Niederberger E | Year | 2023 |
| Journal | FASEB J | Volume | 37 |
| Issue | 12 | Pages | e23287 |
| PubMed ID | 37930651 | Mgi Jnum | J:355497 |
| Mgi Id | MGI:7748863 | Doi | 10.1096/fj.202301489R |
| Citation | Niederberger E, et al. (2023) Distinct molecular mechanisms contribute to the reduction of melanoma growth and tumor pain after systemic and local depletion of alpha-Synuclein in mice. FASEB J 37(12):e23287 |
| abstractText | 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 (alphaSyn/Snca). alphaSyn oligomers accumulate in PD, which triggers typical PD symptoms, and in malignant melanoma, which increases the proliferation of tumor cells. In addition, alphaSyn contributes to non-motor symptoms of PD, including pain. In this study, we investigated the role of alphaSyn in melanoma growth and melanoma-induced pain in a mouse model using systemic and local depletion of alphaSyn. B16BL6 wild-type as well as alphaSyn knock-down melanoma cells were inoculated into the paws of alphaSyn 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 alphaSyn might constitute a promising approach to inhibiting the progression of melanoma and reducing tumor-induced pain. |
