ArticleMolecular brain2016
Regulation of LRRK2 promoter activity and gene expression by Sp1.
Article in Molecular brain, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
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Who cites it
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 20 citations in OpenAlex.
- Competing endogenous RNA (ceRNA) networks in Parkinson's disease: A systematic review.Frontiers in cellular neuroscience · 2023Pooled it
- Unveiling sex-based differences in Parkinson's disease: a comprehensive meta-analysis of transcriptomic studies.Biology of sex differences · 2022Pooled it
- Leucine-rich repeat kinase 2 (LRRK2): balancing cellular homeostasis and Parkinson's disease (PD) pathogenesis.Annals of medicine · 2026Review
- PACS-2 Mitigates NPSC Apoptosis and Intervertebral Disc Degeneration by Preserving MAM Integrity via the SP1/LRRK2/Mfn2 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Microglial Sp1 induced LRRK2 upregulation in response to manganese exposure, and 17β-estradiol afforded protection against this manganese toxicity.Neurotoxicology · 2024Article
- Long noncoding RNAGenes & diseases · 2022Review
- Review
- Article
- The Role of Astrocytes in the Neurorepair Process.Frontiers in cell and developmental biology · 2021Article
- VIP Induces Changes in the F-/G-Actin Ratio of Schlemm's Canal Endothelium via LRRK2 Transcriptional Regulation.Investigative ophthalmology & visual science · 2020Article
- Molecular Cloning and Characterization of Five Glutathione S-Transferase Genes and Promoters fromInsects · 2020Article
- Lipid Metabolism is the common pathologic mechanism between Type 2 Diabetes Mellitus and Parkinson's disease.International journal of medical sciences · 2020Article
- Sp1 in Astrocyte Is Important for Neurite Outgrowth and Synaptogenesis.Molecular neurobiology · 2020Article
- Brain injury induces HIF-1α-dependent transcriptional activation of LRRK2 that exacerbates brain damage.Cell death & disease · 2018Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe dopaminergic neurodegeneration in the nigrostriatal pathway is a prominent neuropathological feature of Parkinson's disease (PD). Mutations in various genes have been linked to familial PD, and leucine-rich repeat kinase 2 (LRRK2) gene is one of them. LRRK2 is a large complex protein, belonging to the ROCO family of proteins. Recent studies suggest that the level of LRRK2 protein is one of the contributing factors to PD pathogenesis. However, it remains elusive how LRRK2 is regulated at the transcriptional and translational level.
resultsIn this study, we cloned a 1738 bp 5'-flanking region of the human LRRK2 gene. The transcriptional start site (TSS) was located to 135 bp upstream of translational start site and the fragment -118 to +133 bp had the minimum promoter activity required for transcription. There were two functional Sp1- responsive elements on the human LRRK2 gene promoter revealed by electrophoretic mobility shift assay (EMSA). Sp1 overexpression promoted LRRK2 transcription and translation in the cellular model. On the contrary, application of mithramycin A inhibited LRRK2 transcriptional and translational activities.
conclusionThis is the first study indicating that Sp1 signaling plays an important role in the regulation of human LRRK2 gene expression. It suggests that controlling LRRK2 level by manipulating Sp1 signaling may be beneficial to attenuate PD-related neuropathology.
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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.