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Article Dans Une Revue Autophagy Année : 2016

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

Résumé

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 tantalising 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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Dates et versions

hal-01287766 , version 1 (14-03-2016)

Identifiants

  • HAL Id : hal-01287766 , version 1
  • PUBMED : 26761717

Citer

Mathieu Bourdenx, Jonathan Daniel, Emilie Genin, Federico N Soria, Mireille Blanchard-Desce, et al.. Nanoparticles restore lysosomal acidification defects: Implication for Parkinson and other lysosomal-related diseases.. Autophagy, 2016. ⟨hal-01287766⟩
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