ArticleOncotarget2017
Activation of the ATF2/CREB-PGC-1α pathway by metformin leads to dopaminergic neuroprotection.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 68 citations in OpenAlex.
- Focused Ultrasound Modulation of PGC-1α Pathways in Neurological Disease: Mechanistic Rationale and Translational Opportunities.Molecular neurobiology · 2026Review
- Metformin beyond Glycemic Control: New Mechanistic Insights and Expanding Therapeutic Horizons.Diabetes & metabolism journal · 2026Review
- Repurposing Antidiabetic Medications for Parkinson's Disease: Focus on Biomarker Strategies for Disease Modification.International journal of molecular sciences · 2026Review
- From Diabetes to Degenerative Diseases: The Multifaceted Action of Metformin.International journal of molecular sciences · 2025Review
- Neuroprotective effects of candesartan in 3-nitropropionic acid-induced Huntington's disease: modulation of angiotensin and CREB/BDNF/PGC1-α signaling.Inflammopharmacology · 2025Article
- Controlling gene expression through five zinc finger domains of ZNF18.Protein science : a publication of the Protein Society · 2025Article
- Repurposing Caffeine, Metformin, and Furosemide to Target Schizophrenia-Related Impairments in a Triple-Hit Rat Model.International journal of molecular sciences · 2025Article
- Combined Administration of Metformin and Propionate Reduces the Degree of Oxidative/Nitrosative Damage of Hypothalamic Neurons in Rat Model of Type 2 Diabetes Mellitus.Molecular neurobiology · 2025Article
- The Possible Role of Metformin and Fibroblast Growth Factor-21 in Multiple Sclerosis Neuropathology: Birds of a Feather Flock Together.The European journal of neuroscience · 2025Review
- Metformin Protects Human Induced Pluripotent Stem Cell (hiPSC)-Derived Neurons from Oxidative Damage Through Antioxidant Mechanisms.Neurotoxicity research · 2025Article
- Neuroprotective Effects of Bifidobacterium animalis subsp. lactis NJ241 in a Mouse Model of Parkinson's Disease: Implications for Gut Microbiota and PGC-1α.Molecular neurobiology · 2024Article
- Isopentyl-Deoxynboquinone Induces Mitochondrial Dysfunction and G2/M Phase Cell Cycle Arrest to Selectively KillAntioxidants & redox signaling · 2024Article
- Metformin role in Parkinson's disease: a double-sword effect.Molecular and cellular biochemistry · 2024Review
- Metformin Treatment Leads to Increased HIV Transcription and Gene Expression through Increased CREB Phosphorylation and Recruitment to the HIV LTR Promoter.Aging and disease · 2024Article
- SinCMat: A single-cell-based method for predicting functional maturation transcription factors.Stem cell reports · 2024Article
- Plausible Role of Mitochondrial DNA Copy Number in Neurodegeneration-a Need for Therapeutic Approach in Parkinson's Disease (PD).Molecular neurobiology · 2023Review
- CaMKK2 as an emerging treatment target for bipolar disorder.Molecular psychiatry · 2023Review
- Restoring autophagic function: a case for type 2 diabetes mellitus drug repurposing in Parkinson's disease.Frontiers in neuroscience · 2023Review
- RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia-an international Delphi consensus.Alzheimer's research & therapy · 2022Review
- Parkinson's Disease and Sugar Intake-Reasons for and Consequences of a Still Unclear Craving.Nutrients · 2022Review
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Progressive dopaminergic neurodegeneration is responsible for the canonical motor deficits in Parkinson's disease (PD). The widely prescribed anti-diabetic medicine metformin is effective in preventing neurodegeneration in animal models; however, despite the significant potential of metformin for treating PD, the therapeutic effects and molecular mechanisms underlying dopaminergic neuroprotection by metformin are largely unknown.In this study, we found that metformin induced substantial proteomic changes, especially in metabolic and mitochondrial pathways in the substantia nigra (SN). Consistent with this data, metformin increased mitochondrial marker proteins in SH-SY5Y neuroblastoma cells. Mitochondrial protein expression by metformin was found to be brain region specific, with metformin increasing mitochondrial proteins in the SN and the striatum, but not the cortex. As a potential upstream regulator of mitochondria gene transcription by metformin, PGC-1α promoter activity was stimulated by metformin via CREB and ATF2 pathways. PGC-1α and phosphorylation of ATF2 and CREB by metformin were selectively increased in the SN and the striatum, but not the cortex. Finally, we showed that metformin protected dopaminergic neurons and improved dopamine-sensitive motor performance in an MPTP-induced PD animal model. Together these results suggest that the metformin-ATF2/CREB-PGC-1α pathway might be promising therapeutic target for PD.
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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.