Estrogen Neuroprotection and Anti-Inflammation Actions in the Hippocampus

The steroid hormone 17β-estradiol (E2) is neuroprotective in several neurodegenerative conditions, including cerebral ischemia, traumatic brain injury, and Alzheimer’s disease (AD). This chapter focuses on the evidence supporting a neuroprotective role of E2 in the hippocampus in cerebral ischemia and AD and reviews various mechanisms thought to underlie E2-induced neuroprotection. Specifically, the chapter discusses the mechanistic role of (a) the various estrogen receptor subtypes, (b) genomic versus nongenomic signaling, (c) regulation of the prosurvival Wnt/β−catenin pathway, and (d) anti-inflammatory effects of E2 in the hippocampus. Finally, we also discuss the role of a novel estrogen receptor co-activator protein, proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) in mediating E2 genomic and non-genomic signaling, as well as the neuroprotective and cognitive-enhancing effects of E2 in the hippocampus.