ArticleMolecular neurodegeneration2022
Melanocortin 1 receptor activation protects against alpha-synuclein pathologies in models of Parkinson's disease.
Article in Molecular neurodegeneration, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Common MC1R Variants and Parkinson Disease Progression.JAMA neurology · 2026Article
- Nrf2 Activators in Parkinson's Disease: Modulating Mitophagy and Regulating Cuproptosis.Molecular neurobiology · 2026Review
- Neural cell state modulation bybioRxiv : the preprint server for biology · 2026Article
- Unlocking Parkinson's disease: harnessing the untapped potential of fatty acid metabolism in disease pathogenesis.Frontiers in immunology · 2026Review
- Article
- Aging disrupts the coordination between mRNA and protein expression in mouse and human midbrain.Molecular psychiatry · 2025Article
- OAB-14 Attenuated Glymphatic System Disorder, Neuroinflammation and Dyskinesia in Parkinson's Disease Model Mice Induced by Rotenone.Neurochemical research · 2025Article
- Nuclear Alpha-Synuclein in Parkinson's Disease and the Malignant Transformation in Melanoma.Neurology research international · 2025Article
- Localization of Melanocortin 1 Receptor in the Substantia Nigra.International journal of molecular sciences · 2024Article
- The Skin-Brain Axis: From UV and Pigmentation to Behaviour Modulation.International journal of molecular sciences · 2024Review
- Aging disrupts the coordination between mRNA and protein expression in mouse and human midbrain.bioRxiv : the preprint server for biology · 2024Article
- Hair color, family history of melanoma, and the risk of Parkinson's disease: An analysis update.Parkinsonism & related disorders · 2024Article
- Astragaloside IV Treats Parkinson's Disease by Regulating the Proliferation and Differentiation of NSCs through the SHH-Nurr1 Pathway.Stem cells international · 2024Article
- Anti-angiogenic and antioxidant effects of axitinib in human retinal endothelial cells: implications in diabetic retinopathy.Frontiers in pharmacology · 2024Article
- Melanocortin 1 Receptor (MC1R): Pharmacological and Therapeutic Aspects.International journal of molecular sciences · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundEpidemiological studies suggest a link between the melanoma-related pigmentation gene melanocortin 1 receptor (MC1R) and risk of Parkinson's 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 alpha-synuclein (αSyn), a key player in PD genetics and pathogenesis.
methodsNigral 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 midbrain from patients with PD and unaffected subjects.
resultsTargeted 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 at the tissue level in PD patients.
conclusionOur study supports an interaction between MC1R and αSyn that can be mediated by neuronal MC1R possibly through Nrf2. It provides evidence for MC1R as a therapeutic target and a rationale for development of MC1R-activating strategies for PD.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.