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. Author manuscript; available in PMC: 2015 Feb 1.
Published in final edited form as: Neurobiol Dis. 2013 Oct 2;62:10.1016/j.nbd.2013.09.018. doi: 10.1016/j.nbd.2013.09.018

Figure 4. Schematic representation of atorvastatin-induced BVR-A neuroprotective effects in the parietal cortex of aged beagles.

Figure 4

Aged beagles are a good preclinical model of Alzheimer disease since they naturally develops learning and memory impairments in association with the accumulation of human-sequence Aβ and increased oxidative stress levels (Cotman and Head, 2008; Head et al., 2008) (right side). Atorvastatin increases (i) HO-1 protein levels and (ii) both BVR-A protein levels and phosphorylation on Tyr/Ser/Thr residues in parietal cortex of aged beagles. As a consequence, an increase of its reductase activity (increased bilirubin (BR) production) is observed. Either BVR-A and BR possesses antioxidant features responsible of the reduction of oxidative stress in the parietal cortex, as demonstrated by the negative correlations found between oxidative stress biomarkers levels and (i) BVR-A protein levels or (ii) BVR activity in the same brain area (Barone et al., 2012b). Furthermore BVR-A is associated with an improvement of cognitive functions (learning) following atorvastatin treatment (Barone et al., 2012b). Finally, BVR-A protein levels and pTyr-BVR-A were significantly associated with decreased BACE1 protein levels suggesting a role for BVR-A in Aβ production (Barone et al., 2012b). All these effects contribute to the neuroprotective role of BVR-A in the brain. Arrows, stimulation; dotted lines, inhibition.