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- Title
The Thiazolidinedione Pioglitazone Increases Cholesterol Biosynthetic Gene Expression in Primary Cortical Neurons by a PPARγ-Independent Mechanism.
- Authors
Cocks, Graham; Wilde, Jonathan I.; Graham, Simon J; Bousgouni, Vicky; Virley, David; Lovestone, Simon; Richardson, Jill
- Abstract
In a recent clinical study, the thiazolidinedione (TZD) pioglitazone (Actos™ was reported to preserve cognitive function in patients with mild to moderate Alzheimer's disease and type II diabetes mellitus. TZDs are agonists of the nuclear hormone receptor peroxisome proliferator-activated receptor-γ (PPARγ), are peripheral insulin sensitizers, and have recently been reported to increase mitochondrial biogenesis in the central nervous system and dendritic spine density. We report a transcriptional profile of the TZD pioglitazone and the non-TZD PPARγ agonist GW347845 in primary cortical culture. We observed that pioglitazone, but not GW347845, increased cholesterol biosynthetic and lipogenic gene expression after 6 h, and the expression of the cholesterol efflux transporters Abca1 and Abcg1 after 24 h. Co-treatment of pioglitazone with the PPARγ antagonist GW9662 did not significantly reduce these effects, suggesting a PPARγ-independent mechanism. These findings suggest a novel effect of TZDs in neurons that may be of relevance as a novel approach against Alzheimer's disease.
- Subjects
CHOLESTEROL; GENE expression; NEURONS; ALZHEIMER'S disease; BIOSYNTHESIS
- Publication
Journal of Alzheimer's Disease, 2010, Vol 19, Issue 2, p631
- ISSN
1387-2877
- Publication type
Article
- DOI
10.3233/JAD-2010-1266