Affiliations: [a] Department of Quantitative Expression, Division of Genetics Research, GlaxoSmithKline, Research Triangle Park, NC, USA | [b] Department of Comparative Genomics, Division of Genetics Research, GlaxoSmithKline, Research Triangle Park, NC, USA | [c] Department of NGI CEDD, Division of Genetics Research, GlaxoSmithKline, Research Triangle Park, NC, USA | [d] Department of Disease and Biomarker Transciptomics, Division of Genetics Research, GlaxoSmithKline, Research Triangle Park, NC, USA | [e] Department of Disease and Biomarker Proteomics, Division of Genetics Research, GlaxoSmithKline, Research Triangle Park, NC, USA | [f] Department of Discovery Pipeline Genetics, Division of Genetics Research, GlaxoSmithKline, Research Triangle Park, NC, USA
Correspondence:
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Corresponding author: Jay C. Strum, Ph.D., Department of Quantitative Expression, Five Moore Drive, GlaxoSmithKline, Research Triangle Park, NC 27278, USA. Tel.: +919 483 5144; Fax: +919 315 0158; E-mail: Jay.C.Strum@gsk.com
Abstract: Rosiglitazone was found to simulate mitochondrial biogenesis in mouse brain in an apolipoprotein (Apo) E isozyme-independent manner. Rosiglitazone induced both mitochondrial DNA (mtDNA) and estrogen-stimulated related receptor alpha (ESRRA) mRNA, a key regulator of mitochondrial biogenesis. Transcriptomics and proteomics analysis suggested the mitochondria produced in the presence of human ApoE3 and E4 were not as metabolically efficient as those in the wild type or ApoE knockout mice. Thus, we propose that PPARγ agonism induces neuronal mitochondrial biogenesis and improves glucose utilization leading to improved cellular function and provides mechanistic support for the improvement in cognition observed in treatment of Alzheimer's patients with rosiglitazone.
Keywords: Mitochodrial biogenesis, PPARγ Alzheimer's Disease, rosiglitazone, real time PCR
