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Nanoparticles restore lysosomal acidification defects: Implications for Parkinson and other lysosomal-related diseases

Abstract : Lysosomal impairment causes lysosomal storage disorders (LSD) and is involved in pathogenesis of neurodegenerative diseases, notably Parkinson disease (PD). Strategies enhancing or restoring lysosomal-mediated degradation thus appear as tantalizing disease-modifying therapeutics. Here we demonstrate that poly(DL-lactide-co-glycolide) (PLGA) acidic nanoparticles (aNP) restore impaired lysosomal function in a series of toxin and genetic cellular models of PD, i.e. ATP13A2-mutant or depleted cells or glucocerebrosidase (GBA)-mutant cells, as well as in a genetic model of lysosomal-related myopathy. We show that PLGA-aNP are transported to the lysosome within 24 h, lower lysosomal pH and rescue chloroquine (CQ)-induced toxicity. Re-acidification of defective lysosomes following PLGA-aNP treatment restores lysosomal function in different pathological contexts. Finally, our results show that PLGA-aNP may be detected after intracerebral injection in neurons and attenuate PD-related neurodegeneration in vivo by mechanisms involving a rescue of compromised lysosomes.
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https://www.hal.inserm.fr/inserm-02439394
Contributor : Benjamin Dehay <>
Submitted on : Tuesday, January 14, 2020 - 3:48:17 PM
Last modification on : Saturday, January 18, 2020 - 1:44:48 AM

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Mathieu Bourdenx, Jonathan Daniel, Emilie Genin, Federico Soria, Mireille Blanchard-Desce, et al.. Nanoparticles restore lysosomal acidification defects: Implications for Parkinson and other lysosomal-related diseases. Autophagy, Taylor & Francis, 2016, 12 (3), pp.472-483. ⟨10.1080/15548627.2015.1136769⟩. ⟨inserm-02439394⟩

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