ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Functional neuroprotection and efficient regulation of GDNF using destabilizing domains in a rodent model of Parkinson's disease.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 59 citations in OpenAlex.
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- FURIN Stimulates NOTCH2 and NOTCH3 Pathways, Leading to Return of Function in Aged Cells.Life (Basel, Switzerland) · 2026Article
- Novel cell-based assay enables FRET-based measurements of the dimerization activity of the chaperone DNAJB6.Biology methods & protocols · 2026Article
- Application of Neurotrophic Factors as a Therapeutic Approach for Neurodegenerative Diseases.Experimental neurobiology · 2025Review
- A systematic screening assay identifies efficient small guide RNAs for CRISPR activation.Frontiers in bioengineering and biotechnology · 2025Article
- Oxidative stress induced by sustained supraphysiological intrastriatal GDNF delivery is prevented by dose regulation.Molecular therapy. Methods & clinical development · 2023Article
- Development of a New DHFR-Based Destabilizing Domain with Enhanced Basal Turnover and Applicability in Mammalian Systems.ACS chemical biology · 2022Article
- Gene-Based Therapeutics for Parkinson's Disease.Biomedicines · 2022Review
- Utility of the DHFR-based destabilizing domain across mouse models of retinal degeneration and aging.iScience · 2022Article
- Regulation of protein secretion through chemical regulation of endoplasmic reticulum retention signal cleavage.Nature communications · 2022Article
- Aβ/Amyloid Precursor Protein-Induced Hyperexcitability and Dysregulation of Homeostatic Synaptic Plasticity in Neuron Models of Alzheimer's Disease.Frontiers in aging neuroscience · 2022Article
- Gene Therapy Approach with an Emphasis on Growth Factors: Theoretical and Clinical Outcomes in Neurodegenerative Diseases.Molecular neurobiology · 2022Review
- Protocol forSTAR protocols · 2020Article
- A Conditional Protein Degradation System To Study Essential Gene Function in Cryptosporidium parvum.mBio · 2020Article
- Simultaneous Control of Endogenous and User-Defined Genetic Pathways Using Unique ecDHFR Pharmacological Chaperones.Cell chemical biology · 2020Article
- GDNF, A Neuron-Derived Factor Upregulated in Glial Cells during Disease.Journal of clinical medicine · 2020Review
- Development and Validation of CRISPR Activator Systems for Overexpression of CB1 Receptors in Neurons.Frontiers in molecular neuroscience · 2020Article
- Regional Differences in Penetration of the Protein Stabilizer Trimethoprim (TMP) in the Rat Central Nervous System.Frontiers in molecular neuroscience · 2020Article
- Non-antibiotic Small-Molecule Regulation of DHFR-Based Destabilizing DomainsMolecular therapy. Methods & clinical development · 2019Article
- GDNF-mediated rescue of the nigrostriatal system depends on the degree of degeneration.Gene therapy · 2019Article
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
Glial cell line-derived neurotrophic factor (GDNF) has great potential to treat Parkinson's disease (PD). However, constitutive expression of GDNF can over time lead to side effects. Therefore, it would be useful to regulate GDNF expression. Recently, a new gene inducible system using destabilizing domains (DD) from E. coli dihydrofolate reductase (DHFR) has been developed and characterized. The advantage of this novel DD is that it is regulated by trimethoprim (TMP), a well-characterized drug that crosses the blood-brain barrier and can therefore be used to regulate gene expression in the brain. We have adapted this system to regulate expression of GDNF. A C-terminal fusion of GDNF and a DD with an additional furin cleavage site was able to be efficiently regulated in vitro, properly processed and was able to bind to canonical GDNF receptors, inducing a signaling cascade response in target cells. In vivo characterization of the protein showed that it could be efficiently induced by TMP and it was only functional when gene expression was turned on. Further characterization in a rodent model of PD showed that the regulated GDNF protected neurons, improved motor behavior of animals and was efficiently regulated in a pathological setting.
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