ArticleCNS neuroscience & therapeutics2024
Exploring the Synergistic Effects of Erinacines on Microglial Regulation and Alzheimer's Pathology Under Metabolic Stress.
Article in CNS neuroscience & therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Recent Advances in Erinacine A: Preparation, Biological Activities, and Biosynthetic Pathway.Molecules (Basel, Switzerland) · 2026Review
- Natural Neuroinflammatory Modulators: Therapeutic Potential of Fungi-Derived Compounds in Selected Neurodegenerative Diseases.Molecules (Basel, Switzerland) · 2025Review
- Ginsenoside C-K inhibits Aβ oligomer-induced Alzheimer's disease pathology progression by regulating microglia-neuron interactions.IBRO neuroscience reports · 2025Article
- Lion's Mane Mushroom (Nutrients · 2025Review
- NeuproGemp, a polyphenol-rich botanical formula, ameliorates Alzheimer's-like pathology in APP/PS1 mice via inhibition of human glutaminyl cyclase.Frontiers in pharmacology · 2025Article
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Authors and funding
9 authors.
Funding
Abstract
backgroundHericium erinaceus mycelium and its constituents, erinacines A and S, have shown neuroprotective effects in APP/PS1 transgenic mice; however, the precise mechanisms by which they modulate microglial phenotypes remain unclear. Our study is the first to explore the effect of erinacines on microglia morphology and the underlying mechanisms using a novel primary mixed glia cell model and advanced bioinformatic tools. Furthermore, we emphasize the clinical relevance by evaluating erinacines in a metabolically stressed APP/PS1 mouse model, which more accurately reflects the complexities of human Alzheimer's disease (AD), where metabolic syndrome is a common comorbidity.
methodsRat primary mixed glial cultures were used to simulate the spectrum of microglial phenotypes, particularly the transition from immature to mature states. Microarray sequencing, along with Connectivity Map, ConsensusPathDB, and Gene Set Enrichment Analysis, identified pathways influenced by erinacines. The therapeutic efficacy was further evaluated in metabolically stressed APP/PS1 mice.
resultsErinacines significantly promoted the development of a ramified, neuroprotective microglial phenotype. Bioinformatics revealed potential modulation of microglia via histone deacetylase inhibition, actin filament dynamics, and synaptic structure modification-pathways not previously linked to erinacines in AD. Importantly, erinacines significantly lower fasting blood glucose and insulin levels while reducing amyloid-beta plaque burden, suppressing hyperactivated glial responses, and enhancing neurogenesis in the metabolically stressed APP/PS1 mice.
conclusionOur findings demonstrate the dual action of erinacines in modulating microglia morphology and phenotype while providing neuroprotection in a model that closely mimic the complexities of human Alzheimer's disease. Additionally, this study provides the foundation for understanding the potential mechanisms of action of erinacines, highlighting their promise as a novel treatment approach for Alzheimer's, particularly in cases complicated by metabolic dysfunction.
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