Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2017 Jun 20;114(25):E4971-E4977. doi: 10.1073/pnas.1700200114. Epub 2017 Jun 5.

Treatment with diphenyl-pyrazole compound anle138b/c reveals that α-synuclein protects melanoma cells from autophagic cell death.

Author information

1
Laboratory of Cellular Dynamics, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
2
Department of Experimental Neurodegeneration, University Medical Center Göttingen, 37073 Göttingen, Germany.
3
Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Georg-August-University Göttingen, 37073 Göttingen, Germany.
4
Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
5
Center for Neuropathology and Prion Research, Ludwig-Maximilians-University, 81377 Munich, Germany.
6
Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, 37075 Göttingen, Germany.
7
Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany.
8
Department of Experimental Neurodegeneration, University Medical Center Göttingen, 37073 Göttingen, Germany; dbecker@gwdg.de.

Abstract

Recent epidemiological and clinical studies have reported a significantly increased risk for melanoma in people with Parkinson's disease. Because no evidence could be obtained that genetic factors are the reason for the association between these two diseases, we hypothesized that of the three major Parkinson's disease-related proteins-α-synuclein, LRRK2, and Parkin-α-synuclein might be a major link. Our data, presented here, demonstrate that α-synuclein promotes the survival of primary and metastatic melanoma cells, which is the exact opposite of the effect that α-synuclein has on dopaminergic neurons, where its accumulation causes neuronal dysfunction and death. Because this detrimental effect of α-synuclein on neurons can be rescued by the small molecule anle138b, we explored its effect on melanoma cells. We found that treatment with anle138b leads to massive melanoma cell death due to a major dysregulation of autophagy, suggesting that α-synuclein is highly beneficial to advanced melanoma because it ensures that autophagy is maintained at a homeostatic level that promotes and ensures the cell's survival.

KEYWORDS:

Parkinson's disease; autophagy; melanoma; oligomer modulator treatment; α-synuclein

PMID:
28584093
PMCID:
PMC5488931
DOI:
10.1073/pnas.1700200114
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center