. PPARγ/RXRα-induced and CD36-mediated microglial amyloid-β phagocytosis results in cognitive improvement in amyloid precursor protein/presenilin 1 mice. J Neurosci. 2012 Nov 28;32(48):17321-31. PubMed.

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  1. This interesting work from Michael Heneka’s group adds to a growing body of evidence bolstering the potential of PPARγ agonists for the treatment of AD. Even more encouraging, the authors’ PPARγ agonist of choice, DSP-8658, is already in developmental trials for treatment of type 2 diabetes and has shown a favorable safety profile so far. The current authors have gone further, though, by also making a foray into mechanistic biology. Specifically, they have nicely shown that PPARγ stimulation promotes microglial Aβ phagocytosis via the innate immune scavenger receptor, CD36. These beneficial effects on Aβ uptake were further augmented by combined agonism of PPARγ and retinoid X receptors. Finally, treatment of the PSAPP mouse model of accelerated cerebral amyloidosis led to an increase in Aβ phagocytosis by microglia in vivo, mitigation of cerebral amyloidosis, and improvement of cognitive impairment. If this mouse model is representative of the clinical syndrome, then the translational potential of PPARγ agonism is certainly something to be excited about.