ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
AAV transduction of dopamine neurons with constitutively active Rheb protects from neurodegeneration and mediates axon regrowth.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 107 citations in OpenAlex.
- AAV Vector-Mediated Modulation of Signaling Pathways in Neurological Disorders: Insights From Cellular, Animal, and Human Studies.Cell biochemistry and function · 2026Review
- Aminochrome-Induced Disruption of Autophagosome-Lysosome Fusion: Implications for Protein Aggregation in Parkinson's Disease.Antioxidants (Basel, Switzerland) · 2026Article
- Home-Based High-Intensity Interval Training for People With Parkinson's: A Randomized, Controlled, Feasibility Trial.Health science reports · 2025Article
- Intracerebellar upregulation of Rheb(S16H) ameliorates motor dysfunction in mice with SCA2.Acta pharmacologica Sinica · 2025Article
- Inhibition of Granule Cell Dispersion and Seizure Development by Astrocyte Elevated Gene-1 in a Mouse Model of Temporal Lobe Epilepsy.Biomolecules · 2024Article
- STAT3 protects dopaminergic neurons against degeneration in animal model of Parkinson's disease.Brain research · 2024Article
- Unraveling the Role of Ras Homolog Enriched in Brain (Rheb1 and Rheb2): Bridging Neuronal Dynamics and Cancer Pathogenesis through Mechanistic Target of Rapamycin Signaling.International journal of molecular sciences · 2024Review
- Are TrkB receptor agonists the right tool to fulfill the promises for a therapeutic value of the brain-derived neurotrophic factor?Neural regeneration research · 2024Review
- Phosphorylated S6K1 and 4E-BP1 play different roles in constitutively active Rheb-mediated retinal ganglion cell survival and axon regeneration after optic nerve injury.Neural regeneration research · 2023Article
- Involvement of brain-derived neurotrophic factor signaling in the pathogenesis of stress-related brain diseases.Frontiers in molecular neuroscience · 2023Review
- Dopamine neuron morphology and output are differentially controlled by mTORC1 and mTORC2.eLife · 2022Article
- Dysregulation of Human Somatic piRNA Expression in Parkinson's Disease Subtypes and Stages.International journal of molecular sciences · 2022Article
- Huntington's disease phenotypes are improved via mTORC1 modulation by small molecule therapy.PloS one · 2022Article
- Restoring lost nigrostriatal fibers in Parkinson's disease based on clinically-inspired design criteria.Brain research bulletin · 2021Review
- Rheb-mTOR activation rescues Aβ-induced cognitive impairment and memory function by restoring miR-146 activity in glial cells.Molecular therapy. Nucleic acids · 2021Article
- TSC-insensitive Rheb mutations induce oncogenic transformation through a combination of constitutively active mTORC1 signalling and proteome remodelling.Cellular and molecular life sciences : CMLS · 2021Article
- Therapeutic Potential of AAV1-Rheb(S16H) Transduction against Neurodegenerative Diseases.International journal of molecular sciences · 2021Review
- Dopaminergic Dysregulation in Syndromic Autism Spectrum Disorders: Insights From Genetic Mouse Models.Frontiers in neural circuits · 2021Review
- Hesperidin protects against behavioral alterations and loss of dopaminergic neurons in 6-OHDA-lesioned mice: the role of mitochondrial dysfunction and apoptosis.Metabolic brain disease · 2021Article
- Interrogation of kinase genetic interactions provides a global view of PAK1-mediated signal transduction pathways.The Journal of biological chemistry · 2020Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
There are currently no therapies that provide either protection or restoration of neuronal function for adult-onset neurodegenerative diseases such as Parkinson's disease (PD). Many clinical efforts to provide such benefits by infusion of neurotrophic factors have failed, in spite of robust effects in preclinical assessments. One important reason for these failures is the difficulty, due to diffusion limits, of providing these protein molecules in sufficient amounts to the intended cellular targets in the central nervous system. This challenge suggests an alternative approach, that of viral vector transduction to directly activate the intracellular signaling pathways that mediate neurotrophic effects. To this end we have investigated the ability of a constitutively active form of the GTPase Rheb, an important activator of mammalian target of rapamycin (mTor) signaling, to mediate neurotrophic effects in dopamine neurons of the substantia nigra (SN), a population of neurons affected in PD. We find that constitutively active hRheb(S16H) induces many neurotrophic effects in mice, including abilities to both preserve and restore the nigrostriatal dopaminergic axonal projections in a highly destructive neurotoxin model. We conclude that direct viral vector transduction of vulnerable neuronal populations to activate intracellular neurotrophic signaling pathways offers promise for the treatment of neurodegenerative 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.