{
  "abstract": "The pathohistological hallmarks of Parkinson’s disease are aggregated alpha-synuclein and other aggregation-prone proteins (Lewy bodies). Recent studies show mechanistic as well as genetic connections between lysosomal dysfunction and Parkinson’s disease pathology. A direct link between lysosomal function and Parkinson’s disease might be the degradation of alpha-synuclein within the lysosomal system. Progranulin is necessary for maintaining lysosomal function, facilitating the activity of several lysosomal enzymes. Progranulin’s exit from the endoplasmic reticulum and its lysosomal availability depend on an interaction with Prosaposin. AZP2006 (INN: Ezeprogind) is a small lysosomotropic neuroprotective molecule currently in clinical development in Progressive Supranuclear Palsy patients. Its neuroprotective effects involve the Progranulin/Prosaposin complex. In this study, we investigated the neuroprotective effects of AZP2006 in several Parkinson’s-like models (vitro and vivo). We showed that AZP2006 was able to counteract a mitochondrial injury as well as the toxicity of alpha-synuclein preformed fibril spreading. We proved that Progranulin was involved in AZP2006’s neuroprotective action, restoring lysosomal homeostasis and ultimately supporting the health of dopaminergic neurons. In light of this evidence, strategies with the aim of improving Progranulin and Prosaposin levels and activity offer a promising therapeutic approach in the context of proteinopathies such as Parkinson’s disease.",
  "abstract_shown": true,
  "affiliations": [
    "Neuro-Sys, Chemin Départemental, Gardanne, France",
    "Alzprotect, Parc Eurasanté, Loos, France"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Noelle Callizot"
    },
    {
      "affs": [
        1
      ],
      "name": "Georgia Culley"
    },
    {
      "name": "Grace Flower"
    },
    {
      "name": "Laura Rouvière"
    },
    {
      "name": "Véronique De Conto"
    },
    {
      "name": "Alexandre Wojcinski"
    },
    {
      "name": "Catherine Botto"
    },
    {
      "name": "Cecilia Estrella"
    },
    {
      "name": "Alexandre Henriques"
    },
    {
      "name": "Philippe Verwaerde"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f6mqkx9y6sdgb.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0359269",
  "fulltext_url": null,
  "id": "f6mqkx9y6sdgb",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0359269",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2728|Parkinson's Disease Mechanisms and Treatments"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Neurochemistry/Neurochemicals/Dopaminergics"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular structures and organelles/Lysosomes"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular structures and organelles/Vesicles"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Glial cells/Microglial cells"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Neurons"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Neurons/Neuronal dendrites/Neurites"
    ],
    [
      "plos",
      "/Biology and life sciences/Neuroscience/Cellular neuroscience/Neurons"
    ],
    [
      "plos",
      "/Biology and life sciences/Neuroscience/Cellular neuroscience/Neurons/Neuronal dendrites/Neurites"
    ],
    [
      "plos",
      "/Biology and life sciences/Neuroscience/Neurochemistry/Neurochemicals/Dopaminergics"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Neurodegenerative diseases/Movement disorders/Parkinson disease"
    ],
    [
      "plos",
      "/Medicine and health sciences/Neurology/Neurodegenerative diseases/Movement disorders/Parkinson disease"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pharmacology/Drugs/Neuroprotectives"
    ]
  ],
  "openalex": "W7214913899",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0359269&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-30",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/f6mqkx9y6sdgb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:37Z",
      "native_id": "10.1371/journal.pone.0359269",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0359269"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "biology",
      "origin": "plos:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "AZP2006 in Parkinson’s disease models: A promising new neuroprotective treatment involving lysosomal homeostasis and the Progranulin/Prosaposin complex",
  "title_text": "AZP2006 in Parkinson’s disease models: A promising new neuroprotective treatment involving lysosomal homeostasis and the Progranulin/Prosaposin complex",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:37Z",
  "url": "https://research.draconitic.com/paper/f6mqkx9y6sdgb",
  "venue": "PLOS One",
  "versions": []
}