{
  "id": 6431850,
  "title": "Dendrimer Delivered shRNA Targeting the CCL20-CCR6 Axis Suppresses Complement-Mediated Microglial Synaptic Pruning and Ameliorates Chronic Neuroinflammation After Repetitive Traumatic Brain Injury",
  "url": "https://urgent.news/2026/09/09/dendrimer-delivered-shrna-targeting-the-ccl20-ccr6-axis-suppresses",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-09T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.04.748639v1?rss=1"
  },
  "original_language": "en",
  "account": "Repetitive traumatic brain injury (rTBI) leads to lasting microglial activation and chronic inflammation, but the underlying causes of long-term synaptic damage are still unknown. This research identifies the CCL20-CCR6 chemokine pathway as a crucial factor in sustaining microglial activation and complement-induced synaptic loss following rTBI.\n\nProteomic analysis at 30 days post-injury (dpi) revealed a general normalization of complement-related inflammatory and synaptic processes in the cortex and hippocampus, indicating a direct connection between chemokine signaling, microglial activation, and synaptic vulnerability. A novel dendrimer-based shRNA system (shCombo-DPX) was created to target this pathway simultaneously by silencing both CCL20 and CCR6.\n\nWhen administered via intranasal or intravenous routes in rTBI mice, shCombo-DPX reduced CCL20-CCR6 expression, decreased chronic microgliosis and astrogliosis, and inhibited complement activation. The treatment prevented microglial engulfment of synapses, preserved synaptic proteins, restored brain-derived neurotrophic factor (BDNF) levels, and improved motor, anxiety-related, and cognitive functions.\n\nIn studies with microglia-neuron cultures, silencing CCL20 decreased LPS-induced complement signaling, avert synaptic loss, neuronal cell death, and depletion of BDNF. In contrast, introducing recombinant CCL20 triggered dendritic degeneration, caspase-3 activation, microglial reactivity, imbalance in complement regulation, and synaptic injury both in laboratory settings and in live animals.\n\nOverall, these results pinpoint CCL20-CCR6 as a primary initiator of chronic complement-mediated synaptic damage in rTBI and support the use of dendrimer-delivered shRNA therapy as a targeted approach to lessen prolonged neurodegeneration.",
  "summary": "Repetitive traumatic brain injury (rTBI) induces persistent microglial activation and chronic neuroinflammation, yet the upstream signals driving long-term synaptic injury remain unclear. In this study, we identify the CCL20-CCR6 chemokine axis as a critical regulator of sustained microglial activation and complement-dependent synaptic loss after rTBI. Proteomic profiling at 30 days post-injury…",
  "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."
}