ArticleBiomedicines2021
SIRT1-Dependent Upregulation of BDNF in Human Microglia Challenged with Aβ: An Early but Transient Response Rescued by Melatonin.
Article in Biomedicines, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- The Kynurenine Pathway: Unraveling Its Role in Neurological Disorders via Mammalian Cellular Models.International journal of molecular sciences · 2026Review
- Microglial Activation Under Hypoxic Conditions in Early Alzheimer's Disease: Can Natural SIRT1 Activators Be Therapeutic Allies in the Inflammation-Energy Axis?Phytotherapy research : PTR · 2026Review
- HMC3 revealed: how much do these "Microglia" really tell us?Frontiers in immunology · 2026Review
- Hypoxia reverses the early anti-inflammatory microglial response to the β-amyloid peptide: mitochondrial involvement and beneficial roles of melatonin and naringenin.Journal of translational medicine · 2025Article
- The Role of SIRT1-BDNF Signaling Pathway in Fluoride-Induced Toxicity for Glial BV-2 Cells.Biological trace element research · 2025Article
- Brain Neurotrophins and Plant Polyphenols: A Powerful Connection.Molecules (Basel, Switzerland) · 2025Review
- Methamphetamine exposure during gestation and lactation periods impairs the learning and memory of offspring mice, which is reversed by melatonin: the role of oxidative stress and acetylcholinesterase.Research in pharmaceutical sciences · 2025Article
- Neuroendocrine characterization into schizophrenia: norepinephrine and melatonin as promising biomarkers.Frontiers in endocrinology · 2025Article
- The Therapeutic Potential of Melatonin in Alzheimer's Disease: A Comprehensive Review.Current medicinal chemistry · 2025Review
- Age and duration of obesity modulate the inflammatory response and expression of neuroprotective factors in mammalian female brain.Aging cell · 2024Article
- Protective Activity of Melatonin Combinations and Melatonin-Based Hybrid Molecules in Neurodegenerative Diseases.Journal of pineal research · 2024Review
- Lipidomics Analysis of Human HMC3 Microglial Cells in an In Vitro Model of Metabolic Syndrome.Biomolecules · 2024Article
- Harnessing BDNF Signaling to Promote Resilience in Aging.Aging and disease · 2024Review
- Physical Exercise-Induced Activation of NRF2 and BDNF as a Promising Strategy for Ferroptosis Regulation in Parkinson's Disease.Neurochemical research · 2024Review
- Exercise mimetics: a novel strategy to combat neuroinflammation and Alzheimer's disease.Journal of neuroinflammation · 2024Review
- Alzheimer's genes in microglia: a risk worth investigating.Molecular neurodegeneration · 2023Review
- Non-Excitatory Amino Acids, Melatonin, and Free Radicals: Examining the Role in Stroke and Aging.Antioxidants (Basel, Switzerland) · 2023Review
- Molecular Research on Alzheimer's Disease.Biomedicines · 2023Article
- Melatonin Activates Anti-Inflammatory Features in Microglia in a Multicellular Context: Evidence from Organotypic Brain Slices and HMC3 Cells.Biomolecules · 2023Article
- Ozone at low concentration modulates microglial activity in vitro: A multimodal microscopy and biomolecular study.Microscopy research and technique · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Microglia represent a first-line defense in the brain. However, in pathological conditions such as Alzheimer's disease (AD), a pro-inflammatory switch may occur, leading to loss of protective functions. Using the human microglial cell line HMC3, we showed that exposure to low concentrations of β-amyloid peptide 1-42 (Aβ42; 0.2 μM) initially (6 h) upregulated anti-inflammatory markers interleukin (IL)-4, IL-13, and brain-derived neurotrophic factor (BDNF). BDNF increase was prevented by selective inhibition of SIRT1 with EX527 (2 μM). Accordingly, these early effects were accompanied by a significant Aβ42-induced increase of SIRT1 expression, nuclear localization, and activity. SIRT1 modulation involved adenosine monophosphate-regulated kinase (AMPK), which was promptly (30 min) phosphorylated by Aβ42, while the AMPK inhibitor BML-275 (2 μM) attenuated Aβ42-induced SIRT1 increase. Initially observed microglial responses appeared transient, as microglial features changed when exposure to Aβ42 was prolonged (0.2 μM for 72 h). While SIRT1 and BDNF levels were reduced, the expression of inflammatory markers IL-1β and tumor necrosis factor (TNF)-α increased. This coincided with a rise in NF-kB nuclear localization. The effects of melatonin (1 μM) on prolonged microglial exposure to Aβ42 were analyzed for their protective potential. Melatonin was able to prolong SIRT1 and BDNF upregulation, as well as to prevent NF-kB nuclear translocation and acetylation. These effects were sensitive to the melatonin receptor antagonist, luzindole (25 μM). In conclusion, our data define an early microglial defensive response to Aβ42, featuring SIRT1-mediated BDNF upregulation that can be exogenously modulated by melatonin, thus identifying an important target for neuroprotection.
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Registered trials
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 Socratic graph.