2024-03-28T14:22:38Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1169732022-06-16T12:35:06Zcom_10261_38com_10261_5com_10261_11773com_10261_1com_10261_128col_10261_291col_10261_11774col_10261_381
DIGITAL.CSIC
author
Mata, Mario de la
author
Cotán, David
author
Oropesa-Ávila, Manuel
author
Garrido-Maraver, Juan
author
Cordero, Mario D.
author
Villanueva Paz, Marina
author
Delgado Pavón, Ana
author
Alcocer-Gómez, Elísabet
author
Lavera, I. de
author
Ybot, Patricia
author
Zaderenko, Paula
author
Ortiz-Mellet, Carmen
author
García Fernández, José Manuel
author
Sánchez-Alcázar, José Antonio
funder
Ministerio de Sanidad, Servicios Sociales e Igualdad (España)
funder
Ministerio de Economía y Competitividad (España)
funder
Junta de Andalucía
funder
European Commission
funder
Asociación de Enfermos de Patologías Mitocondriales (España)
funder
Fundación Medicamentos Huérfanos y Enfermedades Raras
2015-06-22T11:13:13Z
2015-06-22T11:13:13Z
2015
Scientific Reports 5: 10903 (2015)
2045-2322
http://hdl.handle.net/10261/116973
10.1038/srep10903
http://dx.doi.org/10.13039/501100003751http://dx.doi.org/10.13039/501100003329http://dx.doi.org/10.13039/501100000780http://dx.doi.org/10.13039/501100011011
26045184
Gaucher disease (GD) is caused by mutations in the GBA1 gene, which encodes lysosomal
β -glucocerebrosidase. Homozygosity for the L444P mutation in GBA1 is associated with high
risk of neurological manifestations which are not improved by enzyme replacement therapy.
Alternatively, pharmacological chaperones (PCs) capable of restoring the correct folding and
trafficking of the mutant enzyme represent promising alternative therapies.Here, we report on
how the L444P mutation affects mitochondrial function in primary fibroblast derived from GD
patients. Mitochondrial dysfunction was associated with reduced mitochondrial membrane potential,
increased reactive oxygen species (ROS), mitophagy activation and impaired autophagic flux.
Both abnormalities, mitochondrial dysfunction and deficient β -glucocerebrosidase activity, were
partially restored by supplementation with coenzyme Q10 (CoQ) or a L-idonojirimycin derivative,
N-[N’-(4-adamantan-1-ylcarboxamidobutyl)thiocarbamoyl]-1,6-anhydro-L-idonojirimycin (NAdBTAIJ),
and more markedly by the combination of both treatments. These data suggest that targeting
both mitochondria function by CoQ and protein misfolding by PCs can be promising therapies in neurological forms of GD
eng
openAccess
Pharmacological Chaperones and Coenzyme Q10 Treatment Improves Mutant β-Glucocerebrosidase Activity and Mitochondrial Function in Neuronopathic Forms of Gaucher Disease
artículo
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