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Dissecting Comorbidity between Parkinson's Disease and Melanoma in a Cell Culture Model
Author(s) -
DeleOni Deborah,
Bose Anindita,
Petsko Gregory
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.631.1
Subject(s) - disease , substantia nigra , medicine , parkinson's disease , melanoma , comorbidity , alpha synuclein , melanin , oncology , pathology , cancer research , biology , genetics
Parkinson's disease (PD) is a fatal, common, neurodegenerative disorder that affects up to 10 million people worldwide, and lacks disease altering treatment or prevention. It is the second most common neurodegenerative disease globally and is characterized by loss of dopaminergic neurons initially in the substantia nigra. Epidemiological studies have shown that patients with PD have a higher risk of developing melanoma but a lower risk of developing other cancers. According to published reports, the co‐occurrence of melanoma and PD and vice versa is much higher than expected with an odds ratio up to 6 fold. Interestingly, the risk factors of developing PD increase with a family history of melanoma, lighter skin and hair color. Patients who have a first degree relative with either disease also have an increased risk to develop the other disease. The aim of this project was to study the mechanism of association between PD and melanoma. Melanoma cells (SK‐MEL2) that overexpress wild‐type a‐synuclein (the CNS‐specific protein known to aggregate in the brains of Parkinson's patients) and mutant a‐synuclein (A53T, a point mutation that causes autosomal dominant, inherited Parkinson's disease) were used as a model. Menandione was used to induce oxidative stress in the cells, and expression of a‐synuclein and melanin in these cells by Western Blotting. Immunochemistry was utilized to identify co‐localization of a‐synuclein and melanin in the Golgi and melanosomes. This indicates there are potentially common signaling pathway that could explain the comorbidity between the diseases. In addition, we also report the presence of cytoplasmic a‐synuclein and melanin in the cells, implying a possible common secretion pathways for the two proteins. Our observation of localized a‐synuclein in the lysosomes, ensures future areas of potential importance in the interaction and mechanism of lysosomes and a‐synuclein dissection. Additional testing with other cancer cell lines needs to be carried out to ensure that this observed pattern is seen only in melanoma. 1 WT co‐localization between a‐synuclein, melanin and GolgipEGFPWT transfected SK‐MEL2 cells showing staining of a‐synuclein, melanin, golgin and overlay of all three.2 A53T co‐localization between a‐synuclein, melanin and GolgipEGFPA53T transfected SK‐MEL2 cells showing staining of a‐synuclein, melanin, golgin and overlay of all three.3 WT co‐localization between a‐synuclein, melanin and melanosomespEGFPWT transfected SK‐MEL2 cells showing staining of a‐synuclein, melanin, melanosomes and overlay of all three.4 A53T co‐localization between a‐synuclein, melanin and melanosomespEGFPA53T transfected SK‐MEL2 cells showing staining of a‐synuclein, melanin, melanosomes and overlay of all three.5 WT & A53T co‐localization between a‐synuclein, melanin and tyrosinasepEGFPWT and pEGFPA53T transfected SK‐MEL2 cells showing staining of a‐synuclein, melanin, tyrosine and overlay of all three.