{
  "abstract": "Chaperone-mediated autophagy (CMA), regulated by its lysosomal receptor LAMP2A, is a key pathway for αSynuclein (αSyn) clearance and a direct target of αSyn-related neurotoxicity. Rodent studies show that LAMP2A enhancement reverses neurodegeneration, whereas its deficiency accelerates pathology. To test translational relevance, we examined whether increasing LAMP2A expression in nonhuman primates could mitigate α-synucleinopathy induced by injections of Parkinson's disease patient-derived Lewy body (LB) extract. Increasing LAMP2A expression protected nigral dopaminergic neurons from LB-induced αSyn neurodegeneration, delayed the formation and release of pathology-related αSyn species, and evoked a beneficial effect on motor behavior and on cognitive functions of the primate model. Our findings provide preliminary preclinical evidence supporting CMA enhancement as a therapeutic strategy for αSynucleinopathies.",
  "abstract_shown": true,
  "affiliations": [
    "Univ. de Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, France.",
    "Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), 4, Soranou Efesiou Street, Athens 11527, Greece.",
    "Motac Neuroscience, F-33000 Bordeaux, France.",
    "Neuron Experts SAS, F-13015 Marseille, France.",
    "Brain Repair and Imaging in Neural Systems (B.R.A.I.N.S) Unit, Department of Experimental Medical Science, Lund University, BMC D11, 22184 Lund, Sweden.",
    "DANDRITE–Danish Research Institute of Translational Neuroscience and Department of Biomedicine, University of Aarhus, Aarhus C, Denmark.",
    "Professor of Neurology, First Dept of Neurology, National and Kapodistrian University of Athens Medical School, Athens, Greece."
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 25,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Marie-Laure Arotcarena",
      "orcid": "0000-0002-1306-3700"
    },
    {
      "affs": [
        1
      ],
      "name": "Maria Fouka"
    },
    {
      "affs": [
        1
      ],
      "name": "Elena G. Gialinaki"
    },
    {
      "affs": [
        1
      ],
      "name": "Marianna Giannopoulou"
    },
    {
      "affs": [
        0
      ],
      "name": "Hugo Jadot",
      "orcid": "0009-0008-9979-4125"
    },
    {
      "affs": [
        0
      ],
      "name": "Morgane Darricau"
    },
    {
      "affs": [
        0
      ],
      "name": "Anna Lovisotto"
    },
    {
      "affs": [
        0
      ],
      "name": "Sandra Dovero",
      "orcid": "0000-0002-5781-1328"
    },
    {
      "affs": [
        0
      ],
      "name": "Vincent Planche",
      "orcid": "0000-0003-3713-227X"
    },
    {
      "affs": [
        0
      ],
      "name": "Elio Balpe"
    },
    {
      "affs": [
        0
      ],
      "name": "Melyna Achour"
    },
    {
      "affs": [
        0
      ],
      "name": "Marie-Laure Thiolat",
      "orcid": "0000-0003-2586-756X"
    },
    {
      "affs": [
        0
      ],
      "name": "Nathalie Dutheil",
      "orcid": "0000-0001-9121-217X"
    },
    {
      "affs": [
        2
      ],
      "name": "Qin Li",
      "orcid": "0009-0004-3560-4469"
    },
    {
      "affs": [
        2
      ],
      "name": "Emilie Noe",
      "orcid": "0009-0002-8846-2148"
    },
    {
      "affs": [
        2
      ],
      "name": "Elsa Y. Pioli"
    },
    {
      "affs": [
        3
      ],
      "name": "Karim Harhouri",
      "orcid": "0000-0003-2904-5221"
    },
    {
      "affs": [
        3
      ],
      "name": "Rémy Steinschneider"
    },
    {
      "affs": [
        4
      ],
      "name": "Deniz Kirik",
      "orcid": "0000-0002-1360-1265"
    },
    {
      "affs": [
        5
      ],
      "name": "Nanna M. Jensen",
      "orcid": "0000-0003-1177-5197"
    },
    {
      "affs": [
        5
      ],
      "name": "Poul H. Jensen",
      "orcid": "0000-0002-4439-9020"
    },
    {
      "affs": [
        1,
        6
      ],
      "name": "Leonidas Stefanis",
      "orcid": "0000-0003-3569-8990"
    },
    {
      "affs": [
        0
      ],
      "name": "Erwan Bezard",
      "orcid": "0000-0002-0410-4638"
    },
    {
      "affs": [
        0
      ],
      "name": "Benjamin Dehay",
      "orcid": "0000-0003-1723-9045"
    },
    {
      "affs": [
        1
      ],
      "name": "Maria Xilouri",
      "orcid": "0000-0001-7038-0780"
    }
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  "pmcid": "PMC13721977",
  "pmid": "42962009",
  "published": "2026-10-30",
  "publisher": "American Association for the Advancement of Science (AAAS)",
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  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Neuroscience",
      "subfield": "neuroscience"
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  ],
  "title": "LAMP2A gene therapy mitigates Parkinson’s disease–related pathology in nonhuman primates",
  "title_text": "LAMP2A gene therapy mitigates Parkinson’s disease–related pathology in nonhuman primates",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:22:34Z",
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