ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
Overexpression of TFEB Drives a Pleiotropic Neurotrophic Effect and Prevents Parkinson's Disease-Related Neurodegeneration.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
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- [Occurrence characteristics， neurotoxicity risk， and potential mechanisms of traditional phthalate esters and novel alternatives in indoor dust].Se pu = Chinese journal of chromatography · 2026Article
- Targeting non-apoptotic regulated cell death (RCD) to treat neurodegenerative diseases.Acta pharmaceutica Sinica. B · 2026Review
- TFEB degradation is regulated by an IKK/β-TrCP2 phosphorylation-ubiquitination cascade.Nature communications · 2026Article
- Zinc-Mediated Lysosomal Destabilization Links Mitochondrial Damage to Neuronal Death in a Cellular MPPJournal of neurochemistry · 2026Article
- Identification of KHS-101 as a Transcription Factor EB Activator to Promote α-Synuclein Degradation.International journal of molecular sciences · 2026Article
- Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026Review
- The Fragile Balance: Autophagy's Role in Neurodegenerative Disease Progression.Current neuropharmacology · 2026Review
- Current aspects of targeting cellular senescence for the therapy of neurodegenerative diseases.Frontiers in aging neuroscience · 2025Review
- Unraveling the AKT/ERK cascade and its role in Parkinson disease.Archives of toxicology · 2024Review
- Review
- Invertebrate genetic models of amyotrophic lateral sclerosis.Frontiers in molecular neuroscience · 2024Review
- Novel Insight into Functions of Transcription Factor EB (TFEB) in Alzheimer's Disease and Parkinson's Disease.Aging and disease · 2023Review
- In vivo reduction of age-dependent neuromelanin accumulation mitigates features of Parkinson's disease.Brain : a journal of neurology · 2023Article
- Role of TFEB in Diseases Associated with Lysosomal Dysfunction.Advances in experimental medicine and biology · 2023Article
- Characteristic of molecular subtype based on lysosome-associated genes reveals clinical prognosis and immune infiltration of gastric cancer.Frontiers in oncology · 2023Article
- The regulatory mechanism and therapeutic potential of transcription factor EB in neurodegenerative diseases.CNS neuroscience & therapeutics · 2023Review
- Iron-induced cytotoxicity mediated by endolysosomal TRPML1 channels is reverted by TFEB.Cell death & disease · 2022Article
- MEK1/2 inhibition rescues neurodegeneration by TFEB-mediated activation of autophagic lysosomal function in a model of Alzheimer's Disease.Molecular psychiatry · 2022Article
- Risk factors for motor complications in female patients with Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The possible implication of transcription factor EB (TFEB) as a therapeutic target in Parkinson's disease has gained momentum since it was discovered that TFEB controls lysosomal biogenesis and autophagy and that its activation might counteract lysosomal impairment and protein aggregation. However, the majority of putative direct targets of TFEB described to date is linked to a range of biological processes that are not related to the lysosomal-autophagic system. Here, we assessed the effect of overexpressing TFEB with an adeno-associated viral vector in mouse substantia nigra dopaminergic neurons. We demonstrate that TFEB overexpression drives a previously unknown bona fide neurotrophic effect, giving rise to cell growth, higher tyrosine hydroxylase levels, and increased dopamine release in the striatum. TFEB overexpression induces the activation of the mitogen-activated protein kinase 1/3 (MAPK1/3) and AKT pro-survival pathways, phosphorylation of mTORC1 effectors 4E-binding protein 1 (4E-BP1) and S6 kinase B1 (S6K1), and increased protein synthesis. We show that TFEB overexpression prevents dopaminergic cell loss and counteracts atrophy and the associated protein synthesis decline in the MPTP mouse model of Parkinson's disease. Our results suggest that increasing TFEB activity might prevent neuronal death and restore neuronal function in Parkinson's disease and other neurodegenerative diseases through different mechanisms.
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