{
  "abstract": "Complement-mediated glial inflammation and synaptic injury are increasingly implicated in amyotrophic lateral sclerosis (ALS), but clinically translatable complement-modulating therapies remain limited. Atovaquone (ATQ) is an approved, poorly water-soluble small molecule with reported immunomodulatory activity. We investigated whether ATQ could modulate C1qb or C5aR1-associated pathology and whether lactoferrin (Lf)-derived nanomicelles could improve delivery to the spinal cord. ALS spinal-cord single-cell transcriptomic and pathway-enrichment analyses were combined with screening of an FDA-approved drug library, molecular docking and surface plasmon resonance (SPR). Lf-ATQ nanomicelles were characterised by dynamic light scattering, transmission electron microscopy and fluorescence distribution studies. Complement/inflammasome responses were examined in microglial and motor-neuron-microglia models. Therapeutic effects were evaluated in mice expressing the human superoxide dismutase 1 G93A variant (SOD1G93A) by motor testing, compound muscle action potential recording, histology, immunostaining, western blotting and proteomics. Complement genes, particularly C1qb and C5aR1, were enriched in microglia, whereas glutamatergic-synapse and axon-guidance programmes were negatively enriched. In cellular models and SOD1G93A spinal cord, Lf-ATQ reduced C1qb, NLRP3 and multiple inflammatory mediators, attenuated glial reactivity and altered autophagy-related proteins. Treatment preserved rotarod performance, grip strength, gait parameters, compound muscle action potential amplitude and gastrocnemius morphology. Proteomic analysis indicated remodelling of complement/coagulation, vesicular-transport and synaptic modules. These findings support Lf-ATQ as a central nervous system (CNS) -oriented, complement-regulating nanotherapy candidate for ALS. Direct functional target-inhibition assays, quantitative ATQ pharmacokinetics, long-term safety assessment and validation in non-SOD1 models remain necessary before translational conclusions can be drawn.",
  "abstract_shown": true,
  "affiliations": [
    "College of Pharmacy, Shenzhen Technology University, 518118, P. R. China.",
    "College of Life and Health Sciences, Northeastern University, 110819, P. R. China.",
    "Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Ya-Ning Ding"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Madina Bahati"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Mei-Qi Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Pei-Pei Guan"
    },
    {
      "affs": [
        0
      ],
      "name": "Pu Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9b3ybk4craz8d.bib",
  "cited_by": 0,
  "doi": "10.1016/j.mtbio.2026.103738",
  "fulltext_url": "https://europepmc.org/articles/PMC13694724",
  "id": "9b3ybk4craz8d",
  "issns": [
    "2590-0064"
  ],
  "landing_url": "https://europepmc.org/article/MED/42926777",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2728|Amyotrophic Lateral Sclerosis Research"
    ]
  ],
  "openalex": "W7220979836",
  "pdf_url": "https://europepmc.org/articles/PMC13694724?pdf=render",
  "pmcid": "PMC13694724",
  "pmid": "42926777",
  "published": "2026-10-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9b3ybk4craz8d.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42926777",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42926777"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Amyotrophic Lateral Sclerosis Research",
      "subfield": "neurology"
    }
  ],
  "title": "A CNS-targeted atovaquone nanotherapy mitigates complement activation and neuromuscular degeneration in ALS.",
  "title_text": "A CNS-targeted atovaquone nanotherapy mitigates complement activation and neuromuscular degeneration in ALS.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:18Z",
  "url": "https://research.draconitic.com/paper/9b3ybk4craz8d",
  "venue": "Materials today. Bio",
  "versions": []
}