PPAR Agonists: Potential as Therapeutics for Neovascular Retinopathies
Figure 2
Selective PPAR modulator
(SPPARM) model of PPAR ligand action. PPAR is a multivalent receptor whose ligand binding
domain can accommodate different PPAR ligands. Ligands 1, 2, or 3 (e.g., full agonist, partial agonist, or
SPPARM) are capable of
inducing distinct receptor combinations leading to selective gene expression.
Each ligand-receptor complex assumes a somewhat different three-dimensional
conformation, leading to unique and differential interactions with cofactors,
histones (acetylases/deacetylases), and other transcription factors.
Consequently, each PPAR ligand-receptor
complex leads to a differential, but overlapping, pattern of gene expression.
Thus, each ligand will activate, or repress multiple genes leading to
differential overlapping expression of different sets of genes. (Adapted with permission from: J. M. Olefsky, “Treatment of insulin resistance with peroxisome proliferator-activated receptor gamma agonists.” Journal of Clinical Investigation, vol. 106, no. 4, pp. 467-472, 2000); H. A. Pershadsingh, “Treating the metabolic syndrome using angiotensin receptor antagonists that selectively modulate peroxisome proliferator-activated receptor-gamma.” International Journal of Biochemistry and Cellular Biology, vol. 38, nos 5-6, pp. 766-781, 2006.)
