Red hair, <i>MC1R</i> variants, and risk for Parkinson's disease – a meta‐analysis

Chen, Xiqun; Feng, Danielle; Schwarzschild, Michael A.; Gao, Xiang

doi:10.1002/acn3.381

Cited by 29 publications

(29 citation statements)

References 22 publications

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“…MC1R is present on nerve cells in the brain and is thought to play a neuroprotective role, depending on the genetic variant in which it occurs. A similar relationship was found in the Spanish population for the R160W MC1R variant, but subsequent studies did not confirm the significance of this variant in the genetic background of PD [29].…”

Section: Genetic Basis Of Parkinson's Disease and Melanomamentioning

confidence: 64%

“…It could be similar in the case of neuromelanin, which under certain conditions intensifies oxidation processes, inhibits reducing reactions, damages dopaminergic neurons, and generates inflammation induced by phagocytic cells of microglia [13]. Current knowledge shows that the development of both diseases is influenced by complex genetic background, environmental factors, and oxidative stress [27], which is also confirmed by the last study investigating the role of melanocortin 1 receptor gene (MC1R) in the "red-haired" variant in substantia nigra in mice [29]. The genetic basis of both diseases is presented extensively in the review paper by Inzelberg et al [54] and summarised in Table 1.…”

Section: Discussionmentioning

confidence: 78%

“…This study is the first to show the direct impact of the red-haired variant of the MC1R gene associated with melanoma on the survival of dopaminergic neurons in the brain and may provide evidence for targeting MC1R as a new therapeutic strategy for PD [29,30]. At present, the efficacy of MC1R agonists in acute phototoxic reactions, depigmentation diseases and erythropoietic protoporphyria is being assessed in clinical trials.…”

Section: Genetic Basis Of Parkinson's Disease and Melanomamentioning

confidence: 87%

“…An interesting hypothesis is the linking of the gene polymorphism determining red hair colour as an explanation of the correlation of both diseases, namely variant R151C of melanocortin 1 receptor gene (MC1R), which accounts for a fair skin phenotype with reduced UV protection, contributing to an increased risk of melanoma development with a simultaneously increased incidence of PD [29]. In this variant, arginine at position 151 is replaced with cysteine, and in the case of homozygote of the R151C, Cys/Cys allele, only melanin conditioning the red hair colour is formed [29]. This melanin, called pheomelanin, plays the key pro-oxidative role as a final product of the MC1R gene.…”

Section: Genetic Basis Of Parkinson's Disease and Melanomamentioning

confidence: 99%

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Odd correlation: Parkinson’s disease and melanoma. What is the possible link?

2019

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Parkinson's disease (PD) is a neurodegenerative disorder, characterised by depletion of dopamine in the striatum and loss of melanin-positive, dopaminergic neurons in the substantia nigra. Melanoma is a skin neoplasm arising from epidermal melanocytes. The epidemiology of melanoma focuses on well-known risk factors such as light skin and hair colour, gender, eye pigmentation, and ultraviolet (UV) exposure. Many studies have suggested an association between Parkinson's disease and melanoma. The mechanism underlying the possible connection between PD and melanoma is not clear and has aroused lots of interest. More interesting is that the link between these two diseases runs both ways. What is the underlying cause of this reciprocal association?Is it due to Parkinson's treatment? Is levodopa the reason for increased incidence of melanoma in people with the neurodegenerative condition? Are there any genetic, immune system irregularities or environmental risk factors that serve as the common denominator between these two conditions? Should we consider melanoma comorbidity with Parkinson's disease and vice versa? Some hypotheses include pigmentation changes in melanin and/or melanin synthesis enzyme like tyrosinase hydroxylase, autophagy deficits, disturbed form of metabolically controlled cell death, and changes of PD-related genes such as Parkin or a-synuclein. Learning more about the relationship between PD and melanoma may lead to a better understanding of each disease and contribute to more effective treatments of both.

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Section: Genetic Basis Of Parkinson's Disease and Melanomamentioning

confidence: 64%

Section: Discussionmentioning

confidence: 78%

Section: Genetic Basis Of Parkinson's Disease and Melanomamentioning

confidence: 87%

Section: Genetic Basis Of Parkinson's Disease and Melanomamentioning

confidence: 99%

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Odd correlation: Parkinson’s disease and melanoma. What is the possible link?

2019

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“…Scalp hair trace element content has been used to diagnose multiple sclerosis [61]. Also, red hair phenotypes have been associated with greater risk for Parkinson's disease [62]. Further molecular studies are needed to explore noninvasive diagnostic in the field of neurodegenerative medicine.…”

Section: Neurodegenerative Diseases (Nd)mentioning

confidence: 99%

Human Hair as a Testing Substrate in the Era of Precision Medicine: Potential Role of ‘Omics-Based Approaches

Adeola¹,

Wyk²,

Arowolo³

et al. 2018

Keratin

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Minimally and noninvasive investigation of pathology and treatment monitoring is highly attractive in medicine. The use of human hair samples as a non-invasive testing substrate is potentially poised to improve diagnostic and forensic medicine. Hair has the unique ability to capture long-term information about health and disease in an individual as compared to urine and blood. Testing long hair offers a potential means of long-term monitoring of drug compliance, drug abuse, chronic alcohol abuse, and diagnostic biomarker discovery. Even though human hair is mostly composed of keratin and keratin-associated proteins, very little literature has been published on human hair proteomics. Emerging high throughput omics based techniques such as proteomics are increasingly improving our depth of knowledge about the diagnosis, prognosis and prediction of diseases globally. Although many aspects of the use of these novel molecular aids to improve disease diagnosis and patient management remains elusive; it is evident that these techniques have improved precision medicine tremendously. This chapter aims to discuss current plausible application of human hair omics-based approaches to the field of pathology, diagnostics and precision/individualized medicine.

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Cancer and Parkinson's Disease: Common Targets, Emerging Hopes

Filippou

Outeiro

2020

Movement Disorders

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Cancer and neurodegeneration are two major leading causes of morbidity and death worldwide. At first sight, the two fields do not seem to share much in common and, if anything, might be placed on opposite ends of a spectrum. Although neurodegeneration results in excessive neuronal cell death, cancer emerges from increased proliferation and resistance to cell death. Therefore, one might expect significant differences in the underlying pathophysiological mechanisms. However, the more we deepen our understanding of these two types of diseases, the more we appreciate the unexpected overlap between them. Although most epidemiological studies support an inverse association between the risk for development of neurodegenerative diseases and cancer, increasing evidence points to a positive correlation between specific types of cancer, like melanoma, and neurodegenerative diseases, like Parkinson's disease (PD). We believe that deciphering the molecular processes and pathways underlying one of these diseases may significantly increase our understanding about the other. Therefore, the identification of novel biomarkers and therapeutic approaches in cancer, may lead to improved diagnosis and treatment of neurodegeneration, and vice versa. In this Viewpoint, we summarize recent findings connecting both diseases and speculate that insights from one disease may inform on mechanisms, and help identify novel biomarkers and targets for intervention, possibly leading to improved management of both diseases. © 2020 International Parkinson and Movement Disorder Society

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Red hair, MC1R variants, and risk for Parkinson's disease – a meta‐analysis

Cited by 29 publications

References 22 publications

Odd correlation: Parkinson’s disease and melanoma. What is the possible link?

Odd correlation: Parkinson’s disease and melanoma. What is the possible link?

Human Hair as a Testing Substrate in the Era of Precision Medicine: Potential Role of ‘Omics-Based Approaches

Cancer and Parkinson's Disease: Common Targets, Emerging Hopes

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