ArticleExperimental neurology2013
Palmitate induces transcriptional regulation of BACE1 and presenilin by STAT3 in neurons mediated by astrocytes.
Article in Experimental neurology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 53 citations in OpenAlex.
- Intranasal administration of neural stem cell-derived extracellular vesicles prevents cognitive decline in both male and female 3×Tg-AD mice by dampening neuroinflammation and epigenetically regulating amyloid β metabolism.Alzheimer's research & therapy · 2026Article
- Elevated BACE1 mRNA Level is Associated with Lower miR-15a-5p and miR-19b-3p Expressions in Peripheral Blood Mononuclear Cells of Patients with Late-Onset Alzheimer's Disease: Wet Lab Results and Bioinformatics Analysis.Molecular neurobiology · 2025Article
- Pathological Calcium Signaling in Traumatic Brain Injury and Alzheimer's Disease: From Acute Neuronal Injury to Chronic Neurodegeneration.International journal of molecular sciences · 2025Review
- Review
- Extracellular Competing Endogenous RNA Networks Reveal Key Regulators of Early Amyloid Pathology Propagation in Alzheimer's Disease.International journal of molecular sciences · 2025Article
- Autoantibodies to BACE1 promote Aβ accumulation and neurodegeneration in Alzheimer's disease.Acta neuropathologica · 2024Article
- Modulation of Small RNA Signatures by Astrocytes on Early Neurodegeneration Stages; Implications for Biomarker Discovery.Life (Basel, Switzerland) · 2022Review
- Tibolone Pre-Treatment Ameliorates the Dysregulation of Protein Translation and Transport Generated by Palmitic Acid-Induced Lipotoxicity in Human Astrocytes: A Label-Free MS-Based Proteomics and Network Analysis.International journal of molecular sciences · 2022Article
- Fatty Acids: An Insight into the Pathogenesis of Neurodegenerative Diseases and Therapeutic Potential.International journal of molecular sciences · 2022Review
- Lipotoxicity reduces DDX58/Rig-1 expression and activity leading to impaired autophagy and cell death.Autophagy · 2022Article
- Role of Calcium Homeostasis in Alzheimer's Disease.Neuropsychiatric disease and treatment · 2022Review
- STAT3 inhibitor mitigates cerebral amyloid angiopathy and parenchymal amyloid plaques while improving cognitive functions and brain networks.Acta neuropathologica communications · 2021Article
- Insights into T-cell dysfunction in Alzheimer's disease.Aging cell · 2021Review
- PIAS3 suppresses damage in an Alzheimer's disease cell model by inducing the STAT3-associated STAT3/Nestin/Nrf2/HO-1 pathway.Molecular medicine (Cambridge, Mass.) · 2021Article
- Targeting the Transnitrosylation Cascade Provides a Novel Therapeutic Strategy for Alzheimer's Disease.Neuroscience bulletin · 2021Article
- Activated STAT3 signaling pathway by ligature-induced periodontitis could contribute to neuroinflammation and cognitive impairment in rats.Journal of neuroinflammation · 2021Article
- Tibolone Ameliorates the Lipotoxic Effect of Palmitic Acid in Normal Human Astrocytes.Neurotoxicity research · 2020Article
- Palmitate-Induced SREBP1 Expression and Activation Underlies the Increased BACE 1 Activity and Amyloid Beta Genesis.Molecular neurobiology · 2019Article
- Palmitic acid is an intracellular signaling molecule involved in disease development.Cellular and molecular life sciences : CMLS · 2019Review
- Involvement of calpain in the neuropathogenesis of Alzheimer's disease.Medicinal research reviews · 2019Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Deregulation of calcium has been implicated in neurodegenerative diseases, including Alzheimer's disease (AD). Previously, we showed that saturated free-fatty acid, palmitate, causes AD-like changes in primary cortical neurons mediated by astrocytes. However, the molecular mechanisms by which conditioned medium from astrocytes cultured in palmitate induce AD-like changes in neurons are unknown. This study demonstrates that this condition medium from astrocytes elevates calcium level in the neurons, which subsequently increases calpain activity, a calcium-dependent protease, leading to enhance p25/Cdk5 activity and phosphorylation and activation of the STAT3 (signal transducer and activator of transcription) transcription factor. Inhibiting calpain or Cdk5 significantly reduces the upregulation in nuclear level of pSTAT3, which we found to transcriptionally regulate both BACE1 and presenilin-1, the latter is a catalytic subunit of γ-secretase. Decreasing pSTAT3 levels reduced the mRNA levels of both BACE1 and presenilin-1 to near control levels. These data demonstrate a signal pathway leading to the activation of STAT3, and the generation of the amyloid peptide. Thus, our results suggest that STAT3 is an important potential therapeutic target of AD pathogenesis.
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