Effects of PPAR on A metabolism. Excessive production
or insufficient clearance of A results in its aggregation and
finally in the formation of amyloid plaques. This process induces the
activation of microglia as well as astrocytes which respond with the secretion
of proinflammatory molecules like NO, cytokines, and prostaglandins developing
the inflammatory phenotype of AD. In addition, cytokines are able to increase
BACE1 activity thereby stimulating A production. PPAR agonists are able to abate both
effects by either transrepress the production of proinflammatory molecules or
directly interfere with the binding of PPAR to a PPRE in the BACE1 gene
promoter.
