ArticleeLife2020
Pathway-specific dysregulation of striatal excitatory synapses by LRRK2 mutations.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 58 citations in OpenAlex.
- Proteomic profiling across early postnatal development of midbrain dopamine axons innervating the dorsal striatum.bioRxiv : the preprint server for biology · 2026Article
- Article
- Leucine-rich repeat kinase 2 impairs the release sites of Parkinson's disease vulnerable dopamine axons.Nature communications · 2026Article
- Parkinson's Disease Patient-Specific Striatum Organoids Show Hallmarks of Increased Inflammation.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- N-acetyl-l-leucine lowers α-synuclein levels and improves synaptic function in Parkinson's disease models.The Journal of clinical investigation · 2026Article
- TEM-based Study of the Phenotype of Astrocytes Differentiated from Induced Pluripotent Stem Cells from a Healthy Donor and a Patient with Parkinson's Disease.Sovremennye tekhnologii v meditsine · 2026Article
- LRRK2 and the fragile synapse: a molecular prelude to Parkinson's disease?The Biochemical journal · 2025Review
- LRRK2 mediates haloperidol-induced changes in indirect pathway striatal projection neurons.Molecular psychiatry · 2025Article
- Leucine-rich repeat kinase 2 impairs the release sites of Parkinson's disease vulnerable dopamine axons.bioRxiv : the preprint server for biology · 2025Article
- Article
- Hydroxytyrosol has a protective effect on the kidneys through dardarin and spexin.Northern clinics of Istanbul · 2025Article
- Molecular and spatial transcriptomic classification of midbrain dopamine neurons and their alterations in a LRRK2bioRxiv : the preprint server for biology · 2024Article
- Parkinson's-linked LRRK2-G2019S derails AMPAR trafficking, mobility, and composition in striatum with cell-type and subunit specificity.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- FOXP1 regulates the development of excitatory synaptic inputs onto striatal neurons and induces phenotypic reversal with reinstatement.Science advances · 2024Article
- Adenosine AInternational journal of molecular sciences · 2024Article
- Cellular and subcellular localization of Rab10 and phospho-T73 Rab10 in the mouse and human brain.Acta neuropathologica communications · 2023Article
- Mitochondrial Dysfunction in Dopaminergic Neurons Derived from Patients with LRRK2- and SNCA-Associated Genetic Forms of Parkinson's Disease.Current issues in molecular biology · 2023Article
- Modeling Parkinson's disease in LRRK2 rodents.Neuronal signaling · 2023Review
- LRRK2 suppresses lysosome degradative activity in macrophages and microglia through MiT-TFE transcription factor inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Trafficking of the glutamate transporter is impaired in LRRK2-related Parkinson's disease.Acta neuropathologica · 2022Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
LRRK2 is a kinase expressed in striatal spiny projection neurons (SPNs), cells which lose dopaminergic input in Parkinson's disease (PD). R1441C and G2019S are the most common pathogenic mutations of LRRK2. How these mutations alter the structure and function of individual synapses on direct and indirect pathway SPNs is unknown and may reveal pre-clinical changes in dopamine-recipient neurons that predispose toward disease. Here, R1441C and G2019S knock-in mice enabled thorough evaluation of dendritic spines and synapses on pathway-identified SPNs. Biochemical synaptic preparations and super-resolution imaging revealed increased levels and altered organization of glutamatergic AMPA receptors in LRRK2 mutants. Relatedly, decreased frequency of miniature excitatory post-synaptic currents accompanied changes in dendritic spine nano-architecture, and single-synapse currents, evaluated using two-photon glutamate uncaging. Overall, LRRK2 mutations reshaped synaptic structure and function, an effect exaggerated in R1441C dSPNs. These data open the possibility of new neuroprotective therapies aimed at SPN synapse function, prior to disease onset.
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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.