Correction of lysosomal dysfunction as a therapeutic strategy for neurodegenerative diseases.
Bioorg Med Chem Lett
; 24(14): 3001-5, 2014 Jul 15.
Article
in En
| MEDLINE
| ID: mdl-24894562
ABSTRACT
Mutations in the gene that encodes the lysosomal enzyme acid ß-glucosidase lead to reduced cellular activity and accumulation of glycosphingolipid substrates, biochemical hallmarks of the lysosomal storage disorder Gaucher disease (GD). Recently such mutations have been identified as risk factors for Parkinson's disease (PD) and related disorders. Both gain-of-function (due to toxic cellular accumulation of mutant enzyme) and loss-of-function (due to accumulation of lipid substrates) hypotheses have been put forth to address the biochemical link between GD and PD. Similarly, links between Alzheimer's disease and other lysosomal enzyme deficiencies have begun to emerge. The use of pharmacological chaperones to restore the cellular trafficking and activity of mutant lysosomal enzymes may offer a novel approach to treat these debilitating neurodegenerative diseases.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Neurodegenerative Diseases
/
Lysosomes
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Year:
2014
Type:
Article