ChloroquineV1, Hal, Curation, bibRecord, 000170

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

Identifieur interne : 000170 ( Hal/Curation ); précédent : 000169; suivant : 000171

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

Auteurs : Mathieu Bourdenx [France] ; Jonathan Daniel [France] ; Emilie Genin [France] ; Federico Soria [France] ; Mireille Blanchard-Desce [France] ; Erwan Bézard [France] ; Benjamin Dehay [France]

Source :

Autophagy [ 1554-8627 ] ; 2016-03-02.

RBID : Hal:inserm-02439394

English descriptors

mix :
- ATP13A2, GBA, Parkinson disease, XMEA, lysosome, nanoparticles, neurodegeneration.

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.

Url:

https://www.hal.inserm.fr/inserm-02439394

DOI: 10.1080/15548627.2015.1136769

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Le document en format XML

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

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

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