ArticleMolecular neurobiology2023
Metformin and Trehalose-Modulated Autophagy Exerts a Neurotherapeutic Effect on Parkinson's Disease.
Article in Molecular neurobiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Repurposing Anticancer Drugs in Parkinson's Treatment: Molecular Pathways Driving Neuroprotection and Therapeutic Advancement.Molecular neurobiology · 2026Review
- Repurposing Antidiabetic Medications for Parkinson's Disease: Focus on Biomarker Strategies for Disease Modification.International journal of molecular sciences · 2026Review
- Sources of Oxidative Stress in Parkinson's Disease: Pathways and Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2026Review
- Research progress on the α-synuclein-lysosome axis in Parkinson's disease: molecular mechanisms of protein aggregation, autophagy dysfunction, and therapeutic targeting.Frontiers in neuroscience · 2026Review
- Metformin modulates survival, oxidative stress, and gene expression in a high-sucrose Drosophila diabetes model.PloS one · 2026Article
- Molecular mechanisms of exercise-induced neuroprotection against Parkinson's disease.Sports medicine and health science · 2026Review
- Plant secondary metabolites exert therapeutic effects by modulating autophagy pathways.Frontiers in plant science · 2026Review
- Protective Functions of β-Alanyl-L-Histidine and Glycyl-L-Histidyl-L-Lysine Glycoconjugates and Copper in Concert.Antioxidants (Basel, Switzerland) · 2025Review
- PRMT5 Aggravates Parkinson's Disease Progression Through the Inhibition of Neuronal Autophagy Through DKK1.Neurochemical research · 2025Article
- miR-133b-3p Mitigates D-Galactose-Induced Hippocampal Neuron Aging Through Autophagy Regulation via the MAPK/ERK Signaling Pathway.Molecular neurobiology · 2025Article
- APOE4 impairs macrophage lipophagy and promotes demyelination of spiral ganglion neurons in mouse cochleae.Cell death discovery · 2025Article
- Article
- Programmed cell death: molecular mechanisms, biological functions, diseases, and therapeutic targets.MedComm · 2024Review
- Trehalose Alleviates D-Galactose-Induced Aging-Related Granulosa Cell Death in Ovaries.International journal of molecular sciences · 2024Article
- SARS-CoV-2 Infection and Alpha-Synucleinopathies: Potential Links and Underlying Mechanisms.International journal of molecular sciences · 2024Review
- Metformin Lysosomal Targeting: A Novel Aspect to Be Investigated for Metformin Repurposing in Neurodegenerative Diseases?International journal of molecular sciences · 2024Review
- Unlocking the Potential: Caloric Restriction, Caloric Restriction Mimetics, and Their Impact on Cancer Prevention and Treatment.Metabolites · 2024Review
- Alimentary Treatment with Trehalose in a Pharmacological Model of Alzheimer's Disease in Mice: Effects of Different Dosages and Treatment Regimens.Pharmaceutics · 2024Article
- Cyclin-dependent kinase 5 (CDK5) inhibitors in Parkinson disease.Journal of cellular and molecular medicine · 2024Review
- Metformin: The Winding Path from Understanding Its Molecular Mechanisms to Proving Therapeutic Benefits in Neurodegenerative Disorders.Pharmaceuticals (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Since the number of aged people will increase in the next years, neurodegenerative diseases, including Parkinson's Disease (PD), will also rise. Recently, we demonstrated that autophagy stimulation with rapamycin decreases dopaminergic neuronal death mediated by oxidative stress in the paraquat (PQ)-induced PD model. Assessing the neurotherapeutic efficacy of autophagy-inducing molecules is critical for preventing or delaying neurodegeneration. Therefore, we evaluated the autophagy inducers metformin and trehalose effect in a PD model. Autophagy induced by both molecules was confirmed in the SH-SY5Y dopaminergic cells by detecting increased LC3-II marker and autophagosome number compared to the control by western blot and transmission electron microscopy. Both autophagy inducers showed an antioxidant effect, improved mitochondrial activity, and decreased dopaminergic cell death induced by PQ. Next, we evaluated the effect of both inducers in vivo. C57BL6 mice were pretreated with metformin or trehalose before PQ administration. Cognitive and motor deteriorated functions in the PD model were evaluated through the nest building and the gait tests and were prevented by metformin and trehalose. Both autophagy inducers significantly reduced the dopaminergic neuronal loss, astrocytosis, and microgliosis induced by PQ. Also, cell death mediated by PQ was prevented by metformin and trehalose, assessed by TUNEL assay. Metformin and trehalose induced autophagy through AMPK phosphorylation and decreased α-synuclein accumulation. Therefore, metformin and trehalose are promising neurotherapeutic autophagy inducers with great potential for treating neurodegenerative diseases such as PD.
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