Nanoparticles restore lysosomal acidification defects: Implications for Parkinson and other lysosomal-related diseases.
Autophagy. 2016-01-13; 12(3): 472-483
DOI: 10.1080/15548627.2015.1136769
Lire sur PubMed
1. Autophagy. 2016;12(3):472-83. doi: 10.1080/15548627.2015.1136769.
Nanoparticles restore lysosomal acidification defects: Implications for Parkinson
and other lysosomal-related diseases.
Bourdenx M(1)(2), Daniel J(3), Genin E(3), Soria FN(1)(2), Blanchard-Desce M(3),
Bezard E(1)(2), Dehay B(1)(2).
Author information:
(1)a University de Bordeaux, Institut des Maladies Neurodégénératives , UMR 5293,
Bordeaux , France.
(2)b CNRS, Institut des Maladies Neurodégénératives , UMR 5293, Bordeaux ,
France.
(3)c University de Bordeaux, Institut des Sciences Moléculaires , UMR 5255,
Talence , France.
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.
DOI: 10.1080/15548627.2015.1136769
PMCID: PMC4835967
PMID: 26761717 [Indexed for MEDLINE]