Amyloids, melanins and oxidative stress in melanomagenesis

Abstract

Melanoma has traditionally been viewed as an ultra-violet (UV) radiation induced malignancy. While UV is a common inducing factor, other endogenous stresses such as metal ion accumulation or the melanin pigment itself, may provide alternative pathways to melanoma progression. Eumelanosomes within melanoma often exhibit disrupted membranes and fragmented pigment which may be due to alterations in their amyloid-based striatial matrix. The melanosomal amyloid can itself be toxic, especially in combination with reactive oxygen species (ROS) and reactive nitrogen species (RNS) generated by endogenous NADPH oxidase (NOX) and nitric oxide synthase (NOS) enzymes; a toxic mix that may initiate melanomagenesis. Further understanding of the loss of the melanosomal organization, the behavior of the exposed melanin, and the induction of ROS/RNS in melanomas may provide critical insights into this deadly disease.

Associations of MC1R Genotype and Patient Phenotypes with BRAF and NRAS Mutations in Melanoma

“…Future work seems necessary to understand at a biologic level the findings of an interaction of MC1R with phenotypes for BRAF V600E melanoma. A carcinogenic effect of pheomelanin for BRAF V600E melanomagenesis could be mediated by metal ions, melanosomal amyloid, reactive oxygen species, or reactive nitrogen species generated by pheomelanin (Liu-Smith et al, 2015, Meyskens et al, 2004). …”

Oxidative stress and antioxidants in the pathophysiology of malignant melanoma

“…However, their existence as specialized organelles is based on the requirement for cells to contain the hazardous process of melanogenesis. As recognized by melanosome and melanin fans, the presence of melanosomal components and melanin in many organ sites (eye, ear, heart) and its association with amyloid in the brain, raises the ante and opens potential new interventions for their exploration in a range of serious neurologic diseases (Liu-Smith et al, 2015).…”

Lentiginoses in polycythemia vera patient: Is there a role forJAK2 (V617F)mutation?

“…[21][22][23] Furthermore, the statement of association of increased ROS with melanocytic disorders 24 suggested our hypothesis that JAK/ ROS/Ras may be an effective pathway in lentiginosis development rather than coincidentality of JAK2 attendance and lentigo formation. For the reason that, when we consider the possible association of the Polycythemia Vera and Lentigine in Phenolyzer (http://phenolyzer.usc.edu/), the most striking gene found to be associated with was JAK2 (Fig.…”