LAMP2A gene therapy mitigates Parkinson’s disease–related pathology in nonhuman primates
Year: 2026
Type: article
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.
Source: Science Advances
Authors: Marie-Laure Arotcarena, Maria Fouka, Elena G. Gialinaki, Marianna Giannopoulou, Hugo Jadot, Morgane Darricau, Anna Lovisotto, Sandra Dovero, Vincent Planche, Elio Balpe, Melyna Achour, Marie-Laure Thiolat, Nathalie Dutheil, Qin Li, Emilie Noe, Elsa Y. Pioli, Karim Harhouri, Rémy Steinschneider, Deniz Kirik, Nanna M. Jensen, Poul H. Jensen, Leonidas Stefanis, Erwan Bezard, Benjamin Dehay, Maria Xilouri
Institutions: Centre National de la Recherche Scientifique, Université de Bordeaux, Institut des Maladies Neurodégénératives, Biomedical Research Foundation of the Academy of Athens, Génétique et biologie du développement, Laboratoire Physiopathologie et Génétique du Neurone et du Muscle, Lund University, Aarhus University, National and Kapodistrian University of Athens
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,500
OpenAlex ID: W7224905231