ArticleBMC biology2018
Parkinson's disease-linked Parkin mutations impair glutamatergic signaling in hippocampal neurons.
Article in BMC biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- Molecular mechanisms of exercise-induced neuroprotection against Parkinson's disease.Sports medicine and health science · 2026Review
- MicroRNAs and synaptic dysfunction in Parkinson's disease.Molecular therapy. Nucleic acids · 2025Review
- Engineering a cell-based orthogonal ubiquitin transfer cascade for profiling the substrates of RBR E3 Parkin.iScience · 2025Article
- The Role of Glutamatergic Neurons in Changes of Synaptic Plasticity Induced by THz Waves.Biomolecules · 2025Article
- Regulation of Synaptic NMDA Receptor Activity by Post-Translational Modifications.Neurochemical research · 2025Review
- NMDA receptor remodeling and nNOS activation in mice after unilateral striatal injury with 6-OHDA.Heliyon · 2024Article
- Upregulated ECM genes and increased synaptic activity in Parkinson's human DA neurons with PINK1/ PRKN mutations.NPJ Parkinson's disease · 2024Article
- Association between copy number variations in parkin (PRKN) and schizophrenia and autism spectrum disorder: A case-control study.Neuropsychopharmacology reports · 2024Article
- The Role of AMPARs Composition and Trafficking in Synaptic Plasticity and Diseases.Cellular and molecular neurobiology · 2022Review
- Reduced synaptic activity and dysregulated extracellular matrix pathways in midbrain neurons from Parkinson's disease patients.NPJ Parkinson's disease · 2022Article
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- Single-cell analysis of gene expression in the substantia nigra pars compacta of a pesticide-induced mouse model of Parkinson's disease.Translational neuroscience · 2022Article
- Semantic and right temporal variant of FTD: Next generation sequencing genetic analysis on a single-center cohort.Frontiers in aging neuroscience · 2022Article
- Historical perspective and progress on protein ubiquitination at glutamatergic synapses.Neuropharmacology · 2021Review
- Nanomedicine for Neurodegenerative Disorders: Focus on Alzheimer's and Parkinson's Diseases.International journal of molecular sciences · 2021Review
- Secreted Amyloid Precursor Protein-Alpha Enhances LTP Through the Synthesis and Trafficking of CaFrontiers in molecular neuroscience · 2021Article
- Molecular Mechanisms Underlying Synaptic and Axon Degeneration in Parkinson's Disease.Frontiers in cellular neuroscience · 2021Article
- Neuronal Plasticity: Neuronal Organization is Associated with Neurological Disorders.Journal of molecular neuroscience : MN · 2020Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundParkinson's disease (PD)-associated E3 ubiquitin ligase Parkin is enriched at glutamatergic synapses, where it ubiquitinates multiple substrates, suggesting that its mutation/loss-of-function could contribute to the etiology of PD by disrupting excitatory neurotransmission. Here, we evaluate the impact of four common PD-associated Parkin point mutations (T240M, R275W, R334C, G430D) on glutamatergic synaptic function in hippocampal neurons.
resultsWe find that expression of these point mutants in cultured hippocampal neurons from Parkin-deficient and Parkin-null backgrounds alters NMDA and AMPA receptor-mediated currents and cell-surface levels and prevents the induction of long-term depression. Mechanistically, we demonstrate that Parkin regulates NMDA receptor trafficking through its ubiquitination of GluN1, and that all four mutants are impaired in this ubiquitinating activity. Furthermore, Parkin regulates synaptic AMPA receptor trafficking via its binding and retention of the postsynaptic scaffold Homer1, and all mutants are similarly impaired in this capacity.
conclusionOur findings demonstrate that pathogenic Parkin mutations disrupt glutamatergic synaptic transmission in hippocampal neurons by impeding NMDA and AMPA receptor trafficking. Such effects may contribute to the pathophysiology of PD in PARK2 patients.
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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.