Fluorescent Parkin Cell-Based Assay Development for the Screening of Drugs against Parkinson Disease.
SLAS Discov
; 22(1): 67-76, 2017 01.
Article
in En
| MEDLINE
| ID: mdl-27703082
Parkinson disease (PD) is a prevalent neurodegenerative disease characterized by selective degeneration of dopaminergic neurons in the substantia nigra, causing tremor and motor impairment. Parkin protein, whose mutants are the cause of Parkinson disease type 2 (PARK2), has been mechanistically linked to the regulation of apoptosis and the turnover of damaged mitochondria. Several studies have implicated aberrant mitochondria as a key contributor to the development of PD. In the attempt to discover new drugs, high-content cell-based assays are becoming more important to mimic the nature of biological processes and their diversifications in diseases and will be essential for lead identification and the optimization of therapeutic candidates. We have developed a novel fluorescence cell-based assay for high-content screening to find compounds that can promote the mitochondrial localization of Parkin without severe mitochondrial damage induction. In this work, this model was used to screen a library of 1280 compounds. After the screening campaign, the positive compounds were chosen for further testing, based on the strength of the initial response and lack of cytotoxicity. These results indicated that this Parkin cell-based assay is a robust (Z' > 0.5) and valid strategy to test potential candidates for preclinical studies.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Parkinson Disease
/
Biological Assay
/
Ubiquitin-Protein Ligases
/
Drug Evaluation, Preclinical
Type of study:
Diagnostic_studies
/
Screening_studies
Limits:
Humans
Language:
En
Journal:
SLAS Discov
Year:
2017
Document type:
Article
Affiliation country:
Spain
Country of publication:
United States