Drug screening to identify suppressors of GFAP expression.
Hum Mol Genet
; 19(16): 3169-78, 2010 Aug 15.
Article
in En
| MEDLINE
| ID: mdl-20538881
ABSTRACT
Glial fibrillary acidic protein (GFAP) is the major intermediate filament protein of astrocytes in the vertebrate central nervous system. Increased levels of GFAP are the hallmark feature of gliosis, a non-specific response of astrocytes to a wide variety of injuries and disorders of the CNS, and also occur in Alexander disease where the initial insult is a mutation within the coding region of GFAP itself. In both settings, excess GFAP may cause or exacerbate astrocyte dysfunction. With the goal of finding drugs that reduce the expression of GFAP, we have devised screens to detect changes in GFAP promoter activity or protein levels in primary cultures of mouse astrocytes in a 96-well format. We have applied these screens to libraries enriched in compounds that are already approved for human use by the FDA. We report that several compounds are active at micromolar levels in suppressing the expression of GFAP. Treatment of mice for 3 weeks with one of these drugs, clomipramine, causes nearly 50% reduction in the levels of GFAP protein in brain.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Astrocytes
/
Glial Fibrillary Acidic Protein
Type of study:
Diagnostic_studies
/
Prognostic_studies
/
Screening_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Hum Mol Genet
Journal subject:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Year:
2010
Document type:
Article
Affiliation country:
United States