SENS PubMed Publication Search
Acidic nanoparticles protect against α-synuclein-induced neurodegeneration through the restoration of lysosomal function
Marie-Laure Arotcarena 1, Federico N Soria 1 2, Anthony Cunha 1 3, Evelyne Doudnikoff 1, Geoffrey Prévot 1 3 4, Jonathan Daniel 5, Mireille Blanchard-Desce 5, Philippe Barthélémy 3, Erwan Bezard 1, Sylvie Crauste-Manciet 3, Benjamin Dehay 1
...We have recently proven that acidic nanoparticles (aNPs) can re-acidify lysosomes and ameliorate neurotoxin-mediated dopaminergic neurodegeneration in mice. However, no lysosome-targeted approach has yet been tested in synucleinopathy models in vivo. Here, we show that aNPs increase α-synuclein degradation through enhancing lysosomal activity in vitro. We further demonstrate in vivo that aNPs protect nigral dopaminergic neurons from cell death, ameliorate α-synuclein pathology, and restore lysosomal function in mice injected with PD patient-derived Lewy body extracts carrying toxic α-synuclein aggregates. Our results support lysosomal re-acidification as a disease-modifying strategy for the treatment of PD and other age-related proteinopathies.