Aβ Oligomers Induce Neurotoxicity: Effects of HDACs and Nrf2 Modulation

Abstract

The 40‐42 amino acid amyloid βpeptide (Aβ) contributes to one of the central neuropathologic features of Alzheimer's disease (AD). Recent evidence suggests that the oligomeric forms of Aβ may play a role in AD. The objective of the present study was to evaluate the morphological and neurochemical effects of oligomers in primary rat neuronal cells. Neuronal cells were exposed to different doses of soluble Aβ oligomers (0‐90 nM) and analyzed for multiple indices of neuronal homeostasis. Our results indicate that Aβ oligomers promote morphological alterations, neurotoxicity and oxidative stress. The effects of histone deacetylase inhibitors and modulators of the Nrf2 pathway were analyzed for their ability to inhibit the toxicity of Aβ oligomers. Our studies indicate a role for Aβ oligomers as mediators multiple aspects of AD pathogenesis and outline the effects of potentially novel therapeutic strategies as mediators of neuroprotection against Aβ oligomer toxicity.This work was supported by a grant from the Alzheimer's Association and NIA (P01AG005119) to Dr. Jeffrey Keller.