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

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.

Blinded RT‐QuIC Analysis of α‐Synuclein Biomarker in Skin Tissue From Parkinson's Disease Patients

“…Furthermore, IHC of skin tissue proved useful for identifying the immunoreactivity of serine-129 phosphorylated αSyn, which is a major hallmark of αSyn pathology. 53,54 However, cutaneous IHC detection suffers from limitations related primarily to insufficient sensitivity but also due to the patchy availability of autonomic nerves in a given section and the need, for some methods, for specialized and idiosyncratic sample processing and slide interpretation. 28,34,[55][56][57][58] Moreover, oligomeric forms of αSyn were detected in the synaptic terminals of skin tissue using a proximal ligation assay with 82% sensitivity and 89% specificity in a recent case-control study.…”

Are Glucosylceramide-Related Sphingolipids Involved in the Increased Risk for Cancer in Gaucher Disease Patients? Review and Hypotheses

“…Intriguingly, PD patients have a higher risk of developing cancer [93], and in particular melanoma [94]. As a matter of fact, melanoma growth was increased in PD mice compared to wild-type mice [95,96]. Several hypotheses have been proposed to explain this finding.…”

Melanoma proteomics suggests functional differences related to mutational status

“…Although there are no significant differences in functional node activities between groups, the PGM provides some biological processes as candidates to be deregulated among subtypes. Despite the fact that there are a node without an assigned function, it is remarkable that this node contains proteins related with lipoprotein metabolism and melanine synthesis, both previously related with melanoma progression 27,28 . What is more, despite the reduced number of samples, the high growth rate in BRAF-mutant tumors suggested by FBA, although it is not statistically significant, agrees with previous observations, as BRAF-mutated tumors are more proliferative 29 .…”