ArticleCNS neuroscience & therapeutics2014
Lenti-GDNF gene therapy protects against Alzheimer's disease-like neuropathology in 3xTg-AD mice and MC65 cells.
Article in CNS neuroscience & therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- Cognitive Decline in Preclinical Alzheimer's Disease: Amyloid-Beta versus Tauopathy.Journal of Alzheimer's disease : JAD · 2018Pooled it
- Astrocyte Mitochondrial UCP4 Reprograms Neuronal Network Oscillations via GDNF-Dependent KCells · 2026Article
- Interplay Between Aging and Glial Cell Dysfunction: Implications for CNS Health.Life (Basel, Switzerland) · 2025Review
- GDNF overexpression in astrocytes enhances branching and partially preserves hippocampal function in an Alzheimer's rat model.Scientific reports · 2025Article
- Review
- Research models to study lewy body dementia.Molecular neurodegeneration · 2025Review
- Reactive Astrocytes Release GDNF to Promote Brain Recovery and Neuronal Survival Following Ischemic Stroke.Neurochemical research · 2025Article
- The promise of gene therapy in common types of dementia.BioImpacts : BI · 2025Review
- A Ketogenic Diet Affects Gut Microbiota by Regulating Gut Microbiota and Promoting Hippocampal TRHR Expression to Combat Seizures.Journal of molecular neuroscience : MN · 2024Article
- In vivo and ex vivo gene therapy for neurodegenerative diseases: a promise for disease modification.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Harnessing Passive Pulsatile Shear Stress for Alzheimer's Disease Prevention and Intervention.Journal of Alzheimer's disease : JAD · 2024Review
- The Essential Role of Astrocytes in Neurodegeneration and Neuroprotection.CNS & neurological disorders drug targets · 2024Review
- Advancements and Challenges in Antiamyloid Therapy for Alzheimer's Disease: A Comprehensive Review.International journal of Alzheimer's disease · 2024Review
- Article
- CRISPR/Cas9 assisted stem cell therapy in Parkinson's disease.Biomaterials research · 2023Review
- Review
- Neurotrophins and Other Growth Factors in the Pathogenesis of Alzheimer's Disease.Life (Basel, Switzerland) · 2023Review
- Neurotrophic Factors as Regenerative Therapy for Neurodegenerative Diseases: Current Status, Challenges and Future Perspectives.International journal of molecular sciences · 2023Review
- Identification of risk genes for Alzheimer's disease by gene embedding.Cell genomics · 2022Article
- Physical Exercise and Health: A Focus on Its Protective Role in Neurodegenerative Diseases.Journal of functional morphology and kinesiology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsGlial cell-derived neurotrophic factor (GDNF) is emerging as a potent neurotrophic factor with therapeutic potential against a range of neurodegenerative conditions including Alzheimer's disease (AD). We assayed the effects of GDNF treatment in AD experimental models through gene-therapy procedures.
methodsRecombinant lentiviral vectors were used to overexpress GDNF gene in hippocampal astrocytes of 3xTg-AD mice in vivo, and also in the MC65 human neuroblastoma that conditionally overexpresses the 99-residue carboxyl-terminal (C99) fragment of the amyloid precursor protein.
resultsAfter 6 months of overexpressing GDNF, 10-month-old 3xTg-AD mice showed preserved learning and memory, while their counterparts transduced with a green fluorescent protein vector showed cognitive loss. GDNF therapy did not significantly reduce amyloid and tau pathology, but rather, induced a potent upregulation of brain-derived neurotrophic factor that may act in concert with GDNF to protect neurons from atrophy and degeneration. MC65 cells overexpressing GDNF showed an abolishment of oxidative stress and cell death that was at least partially mediated by a reduced presence of intracellular C99 and derived amyloid β oligomers.
conclusionsGDNF induced neuroprotection in the AD experimental models used. Lentiviral vectors engineered to overexpress GDNF showed to be safe and effective, both as a potential gene therapy and as a tool to uncover the mechanisms of GDNF neuroprotection, including cross talk between astrocytes and neurons in the injured brain.
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Registered trials
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