ArticleAging cell2024
The SATB1-MIR22-GBA axis mediates glucocerebroside accumulation inducing a cellular senescence-like phenotype in dopaminergic neurons.
Article in Aging cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 25 citations in OpenAlex.
- Extracellular vesicles in senescence-associated chronic lung diseases.Chinese medical journal · 2026Review
- Suppression of ATM kinase signaling accelerates cellular senescence.Stem cell reports · 2026Article
- Epigenetic dynamics of cellular senescence: From mechanistic insights to precision senotherapy.Chinese medical journal · 2026Review
- Epigenetic Regulation of Modulatory Neurotransmitter System Integrity in the Aging Brain: A Scoping Review Across the Lifespan.Life (Basel, Switzerland) · 2026Review
- SATB1 regulates the osteogenic differentiation of PDLSCs via HDAC1 mediated non-histone protein deacetylation and ubiquitination mechanism and through p38 MAPK pathway under hydrogen peroxide-induced senescent conditions.Stem cell research & therapy · 2026Article
- The role of lipid metabolism in neuronal senescence.FEBS open bio · 2026Review
- NLRP3 facilitates α-synuclein-induced dopaminergic neuronal senescence in a mouse model of Parkinson's disease through SATB1/DNA damage/p21 signaling pathway.Acta pharmacologica Sinica · 2026Article
- Human pluripotent stem cell engineering with CRISPR-Cas9 for Parkinson's disease.Experimental & molecular medicine · 2026Review
- SATB1 Exhibits a Protective Role in HAmylin-Oligomer-Induced Neuronal Damage and Cognition Decline.CNS neuroscience & therapeutics · 2026Article
- Systematic profiling reveals distinct senescence signatures and regulators across human brain cell types.Nature communications · 2025Article
- A rat Satb1 truncation causes neurodevelopmental abnormalities recapitulating the symptoms of patients with SATB1 mutations.Acta pharmacologica Sinica · 2025Article
- Investigating the ageing-Parkinson's disease nexus: standardisation of in vitro models and techniques by the PD-AGE network.NPJ Parkinson's disease · 2025Review
- Article
- A transcriptome-based human universal senescence index (hUSI) robustly predicts cellular senescence under various conditions.Nature aging · 2025Article
- Unlocking Parkinson's disease: the role of microRNAs in regulation, diagnosis, and therapy.Apoptosis : an international journal on programmed cell death · 2025Review
- A hypothesis explaining Alzheimer's disease, Parkinson's disease, and dementia with Lewy bodies overlap.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Aging, cellular senescence and Parkinson's disease.Journal of Parkinson's disease · 2025Review
- Regulatory Network Inference of Induced Senescent Midbrain Cell Types Reveals Cell Type-Specific Senescence-Associated Transcriptional Regulators.bioRxiv : the preprint server for biology · 2025Article
- Sox6 and ALDH1A1 Truncation by Asparagine Endopeptidase Defines Selective Neuronal Vulnerability in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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12 authors at 5 institutions in 2 countries.
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Abstract
Idiopathic Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, which is associated with neuroinflammation and reactive gliosis. The underlying cause of PD and the concurrent neuroinflammation are not well understood. In this study, we utilize human and murine neuronal lines, stem cell-derived dopaminergic neurons, and mice to demonstrate that three previously identified genetic risk factors for PD, namely SATB1, MIR22HG, and GBA, are components of a single gene regulatory pathway. Our findings indicate that dysregulation of this pathway leads to the upregulation of glucocerebrosides (GluCer), which triggers a cellular senescence-like phenotype in dopaminergic neurons. Specifically, we discovered that downregulation of the transcriptional repressor SATB1 results in the derepression of the microRNA miR-22-3p, leading to decreased GBA expression and subsequent accumulation of GluCer. Furthermore, our results demonstrate that an increase in GluCer alone is sufficient to impair lysosomal and mitochondrial function, thereby inducing cellular senescence. Dysregulation of the SATB1-MIR22-GBA pathway, observed in both PD patients and normal aging, leads to lysosomal and mitochondrial dysfunction due to the GluCer accumulation, ultimately resulting in a cellular senescence-like phenotype in dopaminergic neurons. Therefore, our study highlights a novel pathway involving three genetic risk factors for PD and provides a potential mechanism for the senescence-induced neuroinflammation and reactive gliosis observed in both PD and normal aging.
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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.