The Presence of Alpha-Synuclein in Skin from Melanoma and Patients with Parkinson's Disease

Mov Disord Clin Pract. 2017 Jun 1;4(5):724-732. doi: 10.1002/mdc3.12494. eCollection Sep-Oct 2017.

Abstract

Background: The misfolding and prion-like propagation of the protein α-synuclein (α-syn) is the leading molecular signature in Parkinson's disease (PD). There is a significant coincidence of PD and melanoma that may suggest a shared pathophysiology. This study compared the presence of α-syn in neural crest-derived tissues, such as nevi, melanoma, skin tags, and skin biopsies from patients with PD and healthy controls.

Methods: Biopsies from participants with PD were obtained from patients from a tertiary referral center for dermatology and neurology in Mexico and a private dermatopathology center in Florida between January 2015 and March 2016. Biopsies from 7 patients with melanoma, 15 with nevi, 9 with skin tags, 8 with PD, and 9 skin biopsies from healthy volunteers were analyzed for immunohistochemical determination of α-syn and tyrosinase. All analyses were performed by pathologists who were blinded with respect to the clinical diagnosis.

Results: In healthy controls, positive α-syn status was restricted to scattered cells in the basal layer of the epidermis and accounted for 1 ± 0.8% of the analyzed area. In patients with PD, there was increased staining for α-syn PD (3.3 ± 2.3%), with a higher percentage of positive cells in nevi (7.7 ± 5.5%) and melanoma (13.6 ± 3.5%). There was no increased staining in skin tags compared with healthy controls.

Conclusion: Patients with PD and melanoma have increased staining for α-syn in their skin. The authors propose that neurons and melanocytes, both derived from neuroectodermal cells, may share protein synthesis and regulation pathways that become dysfunctional in PD and melanoma.

Keywords: Parkinson disease; melanoma; proteinopathies; α‐synuclein.