ArticleCell death discovery2025
Melatonin orchestrates mitochondrial fusion dynamics-mediated WNT/β-catenin signaling to promote dopaminergic neuronal differentiation of human iPS and nerve regeneration in a MPTP-induced mouse model of Parkinson's disease.
Article in Cell death discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Article
- Oral Sodium Hyaluronate Reshapes Gut Microbiota Composition and Suppresses the LPS-TLR4/NF-κB Pathway to Exert Neuroprotection in MPTP-Induced Parkinson's Disease.International journal of molecular sciences · 2026Article
- Oleuropein Attenuates 6-Hydroxydopamine-Induced Cytotoxicity Through Redox Regulation in Differentiated Dopaminergic Neurons: Potential Involvement of RET-Associated Signalling.International journal of molecular sciences · 2026Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Parkinson's disease (PD) is a challenging neurodegenerative disorder. Recently, therapy of neural stem cells (NSCs) derived from human induced pluripotent stem cells (hiPSCs) has emerged as a significant advancement in regenerative medicine. Melatonin (MT), acting as a mitochondrial targeting hormone, exhibits neuroprotective properties in neurodegenerative diseases and modulates stem cell differentiation through mitochondrial dynamics. However, the precise mechanism by which MT influences dopaminergic (DA) neuronal differentiation in hiPSCs through regulating mitochondrial dynamics remains unclear. In this study, we developed and optimized a technical protocol for the in vitro functional neuronal differentiation of hiPSCs. Our findings demonstrate that MT enhances the differentiation potential of hiPSCs toward neuroectoderm and significantly improves the efficiency of NSCs differentiation into DA neurons by more than three times within hiPSCs. Using the specific MT receptor inhibitor, Luzindole, we confirmed its inhibitory effect on MT-mediated promotion of neural differentiation. Mechanistically, we propose that MT enhances functional DA neuron differentiation from hiPSCs by activating mitochondrial dynamics-mediated WNT/β-catenin signaling pathways. Additionally, we elucidated the critical role of mitofusin2 (MFN2) in enhancing the directed differentiation of DA neurons from hiPSCs. In vivo studies validated the efficacy of MT-treated hiPSC-derived DA progenitor cells in regenerating tyrosine hydroxylase (TH)-positive DA neurons and improving motor function in a MPTP-induced mouse model of Parkinson's disease. In conclusion, this study highlights the potential clinical relevance of MT-enhanced differentiation of hiPSCs into DA neurons, offering promising implications for the treatment of PD. Melatonin orchestrates mitochondrial fusion dynamics-mediated WNT/β-catenin signaling to promote dopaminergic neuronal differentiation of human iPS and nerve regeneration in a MPTP-induced mouse model of Parkinson's disease.
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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.