LAMP2A gene therapy mitigates Parkinson's disease-related pathology in nonhuman primates.

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

Published in

Science advances. Volume 12. Issue 44. Pages eaeg1787. Oct 30, 2026. Epub Oct 30, 2026.

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.

PMID:
42962009
Bibliographic data and abstract were imported from PubMed on 31 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.