Widespread dynamic and pleiotropic expression of the melanocortin-1-receptor (MC1R) system is conserved across chick, mouse and human embryonic development

Thomas, Anna; Heux, Pauline; Santos, Chloe; Arulvasan, Wisenave; Solanky, Nita; Carey, Magalie E.; Gerrelli, Dianne; Kinsler, Veronica A.; Etchevers, Heather C.

doi:10.1101/212712

Cited by 2 publications

(2 citation statements)

References 43 publications

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“…5J). Previous studies reported that MC1R is expressed in CNS neurons in late gestation [44] and neuron cultures prepared from C57BL/6J embryos [18]. To characterize αSyn toxicity and the effect of MC1R in primary cortical neurons, cell preparations from WT and MC1R e/e mice were transduced with BiFC αSyn AAV or control venus AAV at day in vitro (DIV)3 and treated with the MC1R agonist NDP-MSH 2 days later.…”

Section: Mc1r Activation Alleviates αSyn Oligomerization and Neurotoxicity By Activating Nrf2 In Vitromentioning

confidence: 99%

Melanocortin 1 Receptor Activation Protects Against Alpha-Synuclein Pathologies in Models of Parkinson's Disease

et al. 2020

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Background: Epidemiological studies suggest a link between the melanoma-related pigmentation gene melanocortin 1 receptor (MC1R) and risk of Parkinson disease (PD). We previously showed that MC1R signaling can facilitate nigrostriatal dopaminergic neuron survival. The present study investigates the neuroprotective potential of MC1R against neurotoxicity induced by alphasynuclein (αSyn), a key player in PD genetics and pathogenesis.Methods: Nigral dopaminergic neuron toxicity induced by local overexpression of aSyn was assessed in mice that have an inactivating mutation of MC1R, overexpress its wild-type transgene, or were treated with MC1R agonists. The role of nuclear factor erythroid 2-related factor 2 (Nrf2) in MC1R-mediated protection against αSyn was characterized in vitro. Furthermore, MC1R expression was determined in human postmortem midbrains from patients with PD and unaffected subjects.Results: Targeted expression of αSyn in the nigrostriatal pathway induced exacerbated synuclein pathologies in MC1R mutant mice, which were accompanied by neuroinflammation and altered Nrf2 responses, and reversed by the human MC1R transgene. Two MC1R agonists were neuroprotective against αSyn-induced dopaminergic neurotoxicity. In vitro experiments showed that Nrf2 was a necessary mediator of MC1R effects. Lastly, MC1R was present in dopaminergic neurons in the human substantia nigra and appeared to be reduced in PD patients. Conclusion:Our study supports an interaction between MC1R and αSyn that can be mediated by neuronal MC1R through Nrf2. It provides evidence for MC1R as a therapeutic target and a rationale for development of MC1R-activating strategies for PD.

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Section: Mc1r Activation Alleviates αSyn Oligomerization and Neurotoxicity By Activating Nrf2 In Vitromentioning

confidence: 99%

Melanocortin 1 Receptor Activation Protects Against Alpha-Synuclein Pathologies in Models of Parkinson's Disease

et al. 2020

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“…Однако экспрессия этого гена в макрофагах, лимфоцитах и других тканях [9] дает основания для рассмотрения роли МКР1-опосредованного пути как защитного механизма клеток и, в частности, нейронов мозга, который, очевидно реализуется при различных воспалительных процессах [10]. Вместе с тем экспрессия Мкр1 выявлена у эмбрионов различных видов позвоночных, что может свидетельствовать о плейотропном эффекте гена Мкр1 для нормального эмбрионального развития организма, что, по-видимому, эволюционно является весьма консервативным свойством [11].…”

Section: Introductionunclassified

Анализ Распределения Меланокортиновых Рецепторов 1-Го Типа В Нейронах Locus Coeruleus Мыши С57bl/6j

Романова¹,

Михайлова²,

Михрина³

2022

Современная Нейробиология: Фундаментальные Исследования И Практические Аспекты

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С помощью двойного флуоресцентного иммуномечения и конфокальной микроскопии проведен анализ распределения меланокортиновых рецепторов 1-го типа (MKР1) в нейронах locus coeruleus самцов и самок мыши C57Bl/6J. Полученные данные демонстрируют иммуноэкспрессию МКР1 в телах норадренергических и ГАМКергических нейронов и отсутствие видимых половых различий. Обсуждаются механизмы влияния меланокортиновых пептидов на функциональную активность норадренергических нейронов через различные пути меланокортиновой сигнализации как через прямое влияние на норадренергические нейроны, так и через влияние на ГАМК-нейроны. Обсуждается протективная роль меланокортинов через МКР1-зависимый путь во влиянии на норадренергические нейроны мозга. Ключевые слова: меланокортиновые рецепторы, норадреналин, ГАМК, нейропротекция.

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Widespread dynamic and pleiotropic expression of the melanocortin-1-receptor (MC1R) system is conserved across chick, mouse and human embryonic development

Abstract: Background: MC1R, a G-protein coupled receptor with high affinity for alpha-melanocyte

Cited by 2 publications

References 43 publications

Melanocortin 1 Receptor Activation Protects Against Alpha-Synuclein Pathologies in Models of Parkinson's Disease

Melanocortin 1 Receptor Activation Protects Against Alpha-Synuclein Pathologies in Models of Parkinson's Disease

Анализ Распределения Меланокортиновых Рецепторов 1-Го Типа В Нейронах Locus Coeruleus Мыши С57bl/6j

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