Other
14 Authors
- Schwarzschild MA,
- Zuo F,
- Chen H,
- Wang Y,
- Logan R,
- Vanderburg CR,
- Robinson K,
- Li H,
- Ya B,
- Fisher DE,
- Chen X,
- Yu Y,
- Maguire M,
- Cai W
| First Author | Chen X | Year | 2017 |
| Journal | Ann Neurol | Volume | 81 |
| Issue | 3 | Pages | 395-406 |
| PubMed ID | 28019657 | Mgi Jnum | J:322720 |
| Mgi Id | MGI:7259926 | Doi | 10.1002/ana.24852 |
| Citation | Chen X, et al. (2017) The melanoma-linked "redhead" MC1R influences dopaminergic neuron survival. Ann Neurol 81(3):395-406 |
| abstractText | OBJECTIVE: Individuals with Parkinson disease are more likely to develop melanoma, and melanoma patients are reciprocally at higher risk of developing Parkinson disease. Melanoma is strongly tied to red hair/fair skin, a phenotype of loss-of-function polymorphisms in the MC1R (melanocortin 1 receptor) gene. Loss-of-function variants of MC1R have also been linked to increased risk of Parkinson disease. The present study is to investigate the role of MC1R in dopaminergic neurons in vivo. METHODS: Genetic and pharmacological approaches were employed to manipulate MC1R, and nigrostriatal dopaminergic integrity was determined by comprehensive behavioral, neurochemical, and neuropathological measures. RESULTS: MC1R(e/e) mice, which carry an inactivating mutation of MC1R and mimic the human redhead phenotype, have compromised nigrostriatal dopaminergic neuronal integrity, and they are more susceptible to dopaminergic neuron toxins 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Furthermore, a selective MC1R agonist protects against MPTP-induced dopaminergic neurotoxicity. INTERPRETATION: Our findings reveal a protective role of MC1R in the nigrostriatal dopaminergic system, and they provide a rationale for MC1R as a potential therapeutic target for Parkinson disease. Together with its established role in melanoma, MC1R may represent a common pathogenic pathway for melanoma and Parkinson disease. Ann Neurol 2017;81:395-406. |
