Neuroprotective Role of Estrogen Receptor-β in Alzheimer's Disease Pathology.

Sex is one of the main risk factors for Alzheimer's disease (AD). Estrogen signaling has thus been implicated as an important factor in the incidence and development of AD. Decreased expression of estrogen receptor-β (ERβ) in female patients with AD has been linked to impaired mitochondrial function and increased markers of oxidative stress. Furthermore, evidence from ERβ-knockout mice suggests that ERβ deficiency increases mitochondrial vulnerability to amyloid-β (Aβ) toxicity, which may contribute to aggravation of AD pathogenesis. Similarly, it has been shown that overexpression of ERβprotects against Aβ-induced cytotoxicity via multiple mechanisms in the absence of 17β-estradiol. The latter finding presents a new strategy for the development of treatments that will selectively activate ERβ in a ligand-independent manner, potentially allowing for efficacious neuroprotection, while avoiding the side effects associated with estrogen replacement therapy. The purpose of the current manuscript is to review the available research on the role of ERβ in pathological cellular events associated with AD. [ABSTRACT FROM AUTHOR]