{
  "abstract": "Background and objective: Alzheimers disease involves imbalanced amyloid-{beta} (A {beta}) production and clearance, supporting investigation of adjuncts to symptomatic treatment. This study evaluated whether methanolic Hericium erinaceus extract could support recovery after A{beta}1-42-induced injury, alone and with donepezil, through modulation of {beta}-secretase (BACE1) activity or autophagy-associated clearance. Methods: Extract composition and BACE1 inhibition were assessed using liquid chromatography-mass spectrometry (LC-MS) and a fluorescence resonance energy transfer assay, respectively. Neuro-2a cells exposed to A{beta}1-42 (2.42 M) for 6 hours received individual or combined treatments for 24 hours. Cell viability was assessed using WST-1, combination interactions using Bliss independence and protein responses using Western blotting with paired bafilomycin A1 conditions across three independent experiments. Results: LC-MS identified ergothioneine and trace hericenone D. The extract produced an apparent concentration-dependent BACE1-inhibitory response (IC50, 69.97 {+/-} 36.10 g/mL) and significantly increased post-injury viability at 40g/mL (150.2 {+/-} 12.11% of the A {beta} induced control; p = 0.0070). Although the full combination matrix was predominantly additive (Bliss score, 1.95), 51.1 M donepezil with 24.9 g/mL extract produced local synergy (score, 34.29) and the highest observed viability. This pair showed the most coordinated directional protein pattern, with lower mean levels of amyloid precursor protein, A{beta}, and BACE1, and p62/A {beta} accumulation following lysosomal blockade. Western blot differences were not statistically significant. Conclusion: These integrated findings support H. erinaceus as a candidate adjunct to donepezil, with possible complementary effects on amyloidogenic processing and intracellular clearance. Further validation of autophagic flux is needed to confirm the proposed dual response. Keywords: Hericium erinaceus; donepezil; BACE1; amyloid- {beta} ; autophagy; combination treatment",
  "abstract_shown": true,
  "affiliations": [
    "University Of The Free State"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "N. Moselakgomo"
    },
    {
      "name": "W. S. Mthethwa"
    },
    {
      "name": "G. Kemp"
    },
    {
      "name": "M. Gryzenhout"
    },
    {
      "name": "S. Van Zyl"
    },
    {
      "name": "C. Ntsapi-Combrink"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8h1p1dyc9dwzc.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.06.757182",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.06.757182v1.full",
  "id": "8h1p1dyc9dwzc",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.06.757182v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "2737|Alzheimer's disease research and treatments"
    ]
  ],
  "openalex": "W7221819505",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.06.757182v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-06",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/8h1p1dyc9dwzc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:51Z",
      "native_id": "10.64898/2026.10.06.757182",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.06.757182v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "The modulatory effects of Hericium erinaceus and donepezil on amyloid accumulation and autophagy-associated clearance in Aβ1-42-induced N2a cells",
  "title_text": "The modulatory effects of Hericium erinaceus and donepezil on amyloid accumulation and autophagy-associated clearance in Aβ1-42-induced N2a cells",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:51Z",
  "url": "https://research.draconitic.com/paper/8h1p1dyc9dwzc",
  "venue": "bioRxiv",
  "versions": []
}