In models of Alzheimer's disease, activation of PPARs in astrocytes is protective against amyloid-β accumulation (Kalinin et al., 2009; Valles et al., 2010; Wang et al., 2010; Benito et al., 2012; Mandrekar-Colucci et al., 2012). Given the well-established effects of PPAR ligands in other cell types, it is not surprising that these effects occur both through astrocytes and microglia (Wang et al., 2010; Mandrekar-Colucci et al., 2012). The ability of astrocytes to attenuate amyloid-β-induced toxicity depends on the activation and presence of PPARs (Valles et al., 2010; Benito et al., 2012). Exposing astrocytes with reduced PPAR expression to amyloid-β exacerbated production of the inflammatory molecules TNFα (tumour necrosis factor α), IL-6, iNOS (inducible nitric oxide synthase), and COX-2 (cyclo-oxygenase 2) compared with wild-type astrocytes (Benito et al., 2012). Furthermore, treating with a PPARα or PPARγ agonist attenuated the increased inflammatory response in amyloid-β-treated astrocytes (Benito et al., 2012). Encouragingly, the reduced amyloid-dependent toxicity led to improved cognition (Mandrekar-Colucci et al., 2012).
