ArticleJournal of inflammation research2021
LRRK2-NFATc2 Pathway Associated with Neuroinflammation May Be a Potential Therapeutic Target for Parkinson's Disease.
Article in Journal of inflammation research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Small-molecule NFAT signaling inhibitor with dual NFATc1/NFATc2 activity and limited calcineurin catalytic inhibition.Archives of pharmacal research · 2026Article
- NRF2 Deletion Results in Mobility Impairment in A53TSyn Model of Synucleinopathy.Antioxidants (Basel, Switzerland) · 2026Article
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Single-nucleus atlas provides insights into changes in the evolution of the pig hippocampus.BMC biology · 2026Article
- Identification of gene expression signatures associated with neuroinflammation in discogenic sciatica using machine learning and experimental validation.Frontiers in genetics · 2026Article
- Integrating polygenic signals and single-cell multiomics identifies cell-type-specific regulomes critical for immune- and aging-related diseases.Nature aging · 2026Article
- The Parkinson's disease-associated LRRK2-G2019S variant restricts serine metabolism, leading to microglial inflammation and dopaminergic neuron degeneration.Journal of neuroinflammation · 2025Article
- An update on the involvement of inflammatory mediators in Parkinson's disease pathogenesis.Archives of toxicology · 2025Review
- Unraveling Dysregulated Cell Signaling Pathways, Genetic and Epigenetic Mysteries of Parkinson's Disease.Molecular neurobiology · 2024Review
- Vocal learning-associated convergent evolution in mammalian proteins and regulatory elements.Science (New York, N.Y.) · 2024Article
- Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases.Archives of toxicology · 2024Review
- Role of dopamine in the pathophysiology of Parkinson's disease.Translational neurodegeneration · 2023Review
- Animal model for high consumption and preference of ethanol and its interplay with high sugar and butter diet, behavior, and neuroimmune system.Frontiers in nutrition · 2023Article
- Incidence of Parkinson disease in North America.NPJ Parkinson's disease · 2022Article
- A "multi-omics" analysis of blood-brain barrier and synaptic dysfunction in APOE4 mice.The Journal of experimental medicine · 2022Article
- Role of Nrf2 in Parkinson's Disease: Toward New Perspectives.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroinflammation plays an important role in the pathogenesis of Parkinson's disease (PD). However, the molecular mechanisms involved in extracellular α‑synuclein-induced proinflammatory microglial responses through Toll-like receptor 2 (TLR2) are unclear. Leucine-rich repeat kinase 2 (LRRK2) is a serine/threonine kinase, and its mutations are closely related to autosomal dominant PD. Recently, Masliah et al characterized a novel-specific neuroinflammation cascade dependent on LRRK2-NFATc2 in microglia activated by neuron-released α-synuclein. LRRK2 selectively phosphorylated and induced nuclear translocation of NFATc2 to activate a neuroinflammation cascade. In this cascade, LRRK2 kinase was activated by neuron-released α-synuclein in microglia via TLR2. Further, NFATc2, as a kinase substrate for LRRK2, was directly phosphorylated, which accelerated nuclear translocation of NFATc2, where cytokine/chemokine gene expression including TNF-α and IL-6 is regulated by NFATc2 transcriptional activity, resulting in a neurotoxic inflammatory environment. Moreover, an abnormal increase of NFATc2 in nuclear was observed in the brains of patients and a mouse model of PD. Additionally, the administration of an LRRK2 inhibitor could ameliorate neuroinflammation, prevent neuronal loss, and improve motor function. Therefore, modulation of LRKK2-NFATc2 signaling cascade might be a potential therapeutic target for the treatment of PD.
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