{
  "id": 3761714,
  "title": "Hyperactivation of the AXL-ICD/SIRT2 axis by Amyloid-β impairs astrocytic autophagic flux and exacerbates neuroinflammation",
  "url": "https://urgent.news/2026/08/27/hyperactivation-of-the-axl-icd-sirt2-axis-by-amyloid-impairs",
  "topic": "science",
  "section": "Science",
  "published": "2026-08-27T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.08.23.746508v1?rss=1"
  },
  "original_language": "en",
  "account": "Amyloid-β (Aβ) plays a key role in Alzheimer's disease by inducing autophagy dysfunction and neuroinflammation in astrocytes. The TAM receptor AXL serves as a molecular conduit linking Aβ sensing to the regulation of autophagy and inflammation in astrocytes. Aβ triggers the cleavage of AXL through γ-secretase, resulting in the generation of a nuclear intracellular domain (AXL-ICD). This AXL-ICD then forms phase-separated condensates and activates autophagy gene transcription through SIRT2-mediated recruitment of the RUVBL1/2-INO80 chromatin-remodeling complex. AXL-ICD also binds to SIRT2's catalytic domain, inhibiting its deacetylase activity and increasing -tubulin acetylation, which distorts microtubule dynamics. Moderate levels of AXL-ICD promote autophagic flux, but excessive accumulation paradoxically leads to microtubule hyperstabilization, impeding autophagosome-lysosome fusion and causing the pathological buildup of autophagosomes and hydrogen peroxide (H2O2). The inhibitory peptide AxSBiP interferes with the AXL-ICD/SIRT2 interaction, restores autophagic flux, lowers plaque accumulation, and normalizes Aβ-induced H2O2 production and astrogliosis in APP/PS1 mice. The researchers suggest that the AXL-ICD/SIRT2 axis presents a promising therapeutic target to reduce Aβ burden and neuroinflammation in Alzheimer's disease.",
  "summary": "Autophagy dysfunction and neuroinflammation are central to Alzheimer's disease (AD), yet how extracellular amyloid-{beta} (A{beta}) couples to impaired autophagic flux and heightened neuroinflammation remains unknown. Here, we identify the TAM receptor AXL as a molecular transducer that couples A{beta} sensing to the regulation of autophagy and neuroinflammation in astrocytes. A{beta} induces…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}