ArticleCells2022
LRRK2 Inhibition Mitigates the Neuroinflammation Caused by TLR2-Specific α-Synuclein and Alleviates Neuroinflammation-Derived Dopaminergic Neuronal Loss.
Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Synthesis and Preclinical Evaluation of [ACS omega · 2026Article
- Role of LRRK2 in physiological activities, diseases, and therapy.Chinese medical journal · 2026Review
- The Multifaceted Role of LRRK2 in Parkinson's Disease.Brain sciences · 2025Review
- The design and development of LRRK2 inhibitors as novel therapeutics for Parkinson's disease.Future medicinal chemistry · 2025Review
- Exploring the hub Genes and Potential Mechanisms of Complement system-related Genes in Parkinson Disease: Based on Transcriptome Sequencing and Mendelian Randomization.Journal of molecular neuroscience : MN · 2024Article
- The immune system in Parkinson's disease: what we know so far.Brain : a journal of neurology · 2024Review
- Therapeutic Effect ofNeuroSci · 2024Article
- Expression of G2019S LRRK2 in Rat Primary Astrocytes Mediates Neurotoxicity and Alters the Dopamine Synthesis Pathway in N27 Cells via Astrocytic Proinflammatory Cytokines and Neurotrophic Factors.Current issues in molecular biology · 2024Article
- The Role of Immune Dysfunction in Parkinson's Disease Development.International journal of molecular sciences · 2023Review
- LRRK2 and Parkinson's disease: from genetics to targeted therapy.Annals of clinical and translational neurology · 2023Review
- Role of α-synuclein in microglia: autophagy and phagocytosis balance neuroinflammation in Parkinson's disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- A proteogenomic view of Parkinson's disease causality and heterogeneity.NPJ Parkinson's disease · 2023Article
- Nuclear α-Synuclein-Derived Cytotoxic Effect via Altered Ribosomal RNA Processing in Primary Mouse Embryonic Fibroblasts.International journal of molecular sciences · 2023Article
- Pathophysiological evaluation of the LRRK2 G2385R risk variant for Parkinson's disease.NPJ Parkinson's disease · 2022Article
- Immune Response Modifications in the Genetic Forms of Parkinson's Disease: What Do We Know?International journal of molecular sciences · 2022Review
- Genetic variations inFrontiers in neurology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Evidence suggests that crosstalk occurs between microglial leucine-rich repeat kinase 2 (LRRK2)-a regulator of neuroinflammation-and neuron-released α-synuclein (αSyn)-a promoter of microglial activation and neuroinflammatory responses-in neuroinflammation-mediated Parkinson's disease (PD) progression. Therefore, we examined whether LRRK2 inhibition reduces the responses of microglia to neuroinflammation caused by neuron-released αSyn. We examined the neuroinflammatory responses provoked by Toll-like receptor 2 (TLR2)-positive αSyn of neuronal cells using an LRRK2 inhibitor in the mouse glioma cells, rat primary microglia, and human microglia cell line; and the effects of LRRK2 inhibitor in the co-culture of ectopic αSyn-expressing human neuroblastoma cells and human microglia cells and in mouse models by injecting αSyn. We analyzed the association between LRRK2 activity and αSyn oligomer and TLR2 levels in the substantia nigra tissues of human patients with idiopathic PD (iPD). The TLR2-specific αSyn elevated LRRK2 activity and neuroinflammation, and the LRRK2 inhibitor ameliorated neuroinflammatory responses in various microglia cells, alleviated neuronal degeneration along with neuroinflammation in the co-culture, and blocked the further progression of locomotor failure and dopaminergic neuronal degeneration caused by TLR2-specific αSyn in mice. Furthermore, LRRK2 phosphorylation was increased in patients with iPD showing αSyn-specific high TLR2 level. These results suggest the application of LRRK2 inhibitors as a novel therapeutic approach against αSyn-mediated PD progression.
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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.