ArticleNeurobiology of aging2013
Palmitate-activated astrocytes via serine palmitoyltransferase increase BACE1 in primary neurons by sphingomyelinases.
Article in Neurobiology of aging, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 70 citations in OpenAlex.
- A Lipid Road to Neuroimmunology: Fatty Acids Linking Immune and Nervous Systems.Neuroimmunomodulation · 2026Review
- Brain interleukins and Alzheimer's disease.Metabolic brain disease · 2025Review
- Amyloid-beta metabolism in age-related neurocardiovascular diseases.European heart journal · 2025Review
- Potential Roles of Hypoxia-Inducible Factor-1 in Alzheimer's Disease: Beneficial or Detrimental?Antioxidants (Basel, Switzerland) · 2024Review
- Combined Metabolic Activators with Different NAD+ Precursors Improve Metabolic Functions in the Animal Models of Neurodegenerative Diseases.Biomedicines · 2024Article
- The Associations of Individual and Subclasses of Nonesterified Fatty Acids With Disability, and Mobility Limitation in Older Adults: The Cardiovascular Health Study.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023Article
- Functional consequences of brain exposure to saturated fatty acids: From energy metabolism and insulin resistance to neuronal damage.Endocrinology, diabetes & metabolism · 2023Review
- Sphingolipid metabolism in brain insulin resistance and neurological diseases.Frontiers in endocrinology · 2023Review
- AVE 0991 Suppresses Astrocyte-Mediated Neuroinflammation of Alzheimer's Disease by Enhancing Autophagy.Journal of inflammation research · 2023Article
- The gut microbiota in neurodegenerative diseases: revisiting possible therapeutic targets for cannabidiol.Heliyon · 2022Review
- Modulation of Small RNA Signatures by Astrocytes on Early Neurodegeneration Stages; Implications for Biomarker Discovery.Life (Basel, Switzerland) · 2022Review
- Metabolomic Analysis of Human Astrocytes in Lipotoxic Condition: Potential Biomarker Identification by Machine Learning Modeling.Biomolecules · 2022Article
- Integrated Metabolomics and Lipidomics Reveal High Accumulation of Glycerophospholipids in Human Astrocytes under the Lipotoxic Effect of Palmitic Acid and Tibolone Protection.International journal of molecular sciences · 2022Article
- Neuroinflammatory Signaling in the Pathogenesis of Alzheimer's Disease.Current neuropharmacology · 2022Review
- The Potential Role of Cytokines and Growth Factors in the Pathogenesis of Alzheimer's Disease.Cells · 2021Review
- Role of Exendin-4 in Brain Insulin Resistance, Mitochondrial Function, and Neurite Outgrowth in Neurons under Palmitic Acid-Induced Oxidative Stress.Antioxidants (Basel, Switzerland) · 2021Article
- Non-Esterified Fatty Acids and Risks of Frailty, Disability, and Mobility Limitation in Older Adults: The Cardiovascular Health Study.Journal of the American Geriatrics Society · 2020Article
- Tibolone Ameliorates the Lipotoxic Effect of Palmitic Acid in Normal Human Astrocytes.Neurotoxicity research · 2020Article
- Review
- Palmitic Acid-Induced NADNeurochemical research · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Astrocytes play a critical role in neurodegenerative diseases, including Alzheimer's disease (AD). Previously, we showed that saturated free fatty acid, palmitic acid (PA), upregulates β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) level and amyloidogenesis in primary rat neurons mediated by astrocytes. However, the molecular mechanisms by which conditioned media from PA-treated astrocytes upregulates BACE1 level in neurons are unknown. This study demonstrates that serine palmitoyltransferase (SPT) in the astrocytes increases ceramide levels, which enhances the release of cytokines that mediate the activation of neural and acidic sphingomyelinase (SMase) in the neurons, to propagate the deleterious effects of PA (i.e., BACE1 upregulation). In support of the relevance of SPT in AD, our laboratory recently measured and found SPT levels to be significantly upregulated in AD brains as compared with controls. Cytokines, namely tumor necrosis factor-α and interleukin-1β, released into the conditioned media of PA-treated astrocytes activate neural and acidic SMase in the neurons. Neutralizing the cytokines in the PA-treated astrocyte conditioned media reduced BACE1 upregulation. However, inhibiting SPT in the astrocytes decreased the levels of both tumor necrosis factor-α and interleukin-1β in the conditioned media, which in turn reduced the SMase activities and BACE1 level in primary neurons. Thus, our results suggest that the activation of the astrocytes by PA is mediated by SPT, and the activated astrocytes increases BACE1 level in the neurons; the latter is mediate by the SMases.
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