ArticleProceedings of the National Academy of Sciences of the United States of America2014
Increased vesicular monoamine transporter enhances dopamine release and opposes Parkinson disease-related neurodegeneration in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers, 1 of them a synthesis that pooled it.
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Who cites it
123 citing papers in PubMed, 1 synthesis or guideline pooled it, 238 citations in OpenAlex.
- Neuroprotective Effects of Resveratrol in In vivo and In vitro Experimental Models of Parkinson's Disease: a Systematic Review.Neurotoxicity research · 2022Pooled it
- VMAT-DAT-Dopamine Regulatory System Involved in the Protective Effect of 3-n-Butylphthalide Against Ischemic Stroke.CNS neuroscience & therapeutics · 2026Article
- Genetic Architecture of Addiction-Relevant Behaviors in Outbred Sprague-Dawley Rats Reveals Loci for Anxiety-Like and Nociceptive Traits.Genes, brain, and behavior · 2026Article
- Neurotransmitter Dysregulation in Parkinson's Disease: Pathophysiological Insights and Therapeutic Perspectives.ACS chemical neuroscience · 2026Review
- Genetic Architecture of Addiction-Relevant Behaviors in Outbred Sprague-Dawley Rats Reveals Loci for Anxiety-Like and Nociceptive Traits.bioRxiv : the preprint server for biology · 2026Article
- VMAT2 dysfunction impairs vesicular dopamine uptake, driving its oxidation and α-synuclein pathology in DJ-1-linked Parkinson's neurons.Science advances · 2026Article
- Evaluation of the Relationship between Vesicular Monoamine Transporter 2 (VMAT2) Inhibition and Neurologic Adverse Events in Approved Drugs.ACS pharmacology & translational science · 2026Article
- Mitochondrial dysfunction and oxidative stress in Parkinson's disease: mechanisms, biomarkers, and therapeutic strategies.Tissue barriers · 2026Review
- Mitochondrial resilience: a convergent framework for pathogenesis and neuroprotection in Parkinson's disease.Frontiers in pharmacology · 2026Review
- Peripheral catecholamine systems: an evolutionary perspective.American journal of physiology. Regulatory, integrative and comparative physiology · 2025Review
- Organic cation transporter 3 on neuronal mitochondria mediates MPPBMC biology · 2025Article
- KGG: a fully automated workflow for creating disease-specific knowledge graphs.Bioinformatics (Oxford, England) · 2025Article
- Bacopaside-I ameliorates motor dysfunction and neurodegeneration in rat model of Parkinson's disease.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Characterization of the Molecular Mechanisms Underlying Lurasidone-Induced Acute Manic Episodes in Bipolar Depression: A Network Pharmacology and Molecular Docking Approach.CNS neuroscience & therapeutics · 2025Article
- HDAC4/5 Inhibitor, LMK-235 Improves Animal Voluntary Movement in MPTP-Induced Parkinson's Disease Model.Pharmacology research & perspectives · 2025Article
- Construction and Identification of Inflammation-Related TF-mRNA-miRNA Coexpression Network and Immune Infiltration in Parkinson's Disease.Parkinson's disease · 2025Article
- Tricyclic and tetracyclic antidepressants upregulate VMAT2 activity and rescue disease-causing VMAT2 variants.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Histamine synthesis and transport are coupled in axon terminals via a dual quality control system.The EMBO journal · 2024Article
- Selective dopaminergic neurotoxicity modulated by inherent cell-type specific neurobiology.Neurotoxicology · 2024Review
- Molecular and cellular mechanisms of selective vulnerability in neurodegenerative diseases.Nature reviews. Neuroscience · 2024Review
63 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
Disruption of neurotransmitter vesicle dynamics (transport, capacity, release) has been implicated in a variety of neurodegenerative and neuropsychiatric conditions. Here, we report a novel mouse model of enhanced vesicular function via bacterial artificial chromosome (BAC)-mediated overexpression of the vesicular monoamine transporter 2 (VMAT2; Slc18a2). A twofold increase in vesicular transport enhances the vesicular capacity for dopamine (56%), dopamine vesicle volume (33%), and basal tissue dopamine levels (21%) in the mouse striatum. The elevated vesicular capacity leads to an increase in stimulated dopamine release (84%) and extracellular dopamine levels (44%). VMAT2-overexpressing mice show improved outcomes on anxiety and depressive-like behaviors and increased basal locomotor activity (41%). Finally, these mice exhibit significant protection from neurotoxic insult by the dopaminergic toxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), as measured by reduced dopamine terminal damage and substantia nigra pars compacta cell loss. The increased release of dopamine and neuroprotection from MPTP toxicity in the VMAT2-overexpressing mice suggest that interventions aimed at enhancing vesicular capacity may be of therapeutic benefit in Parkinson 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.