Heat Shock Protein 70 Participates in the Neuroprotective Response to Intracellularly Expressed β-Amyloid in Neurons
Open Access
- 18 February 2004
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 24 (7) , 1700-1706
- https://doi.org/10.1523/jneurosci.4330-03.2004
Abstract
Intracellular β-amyloid 42 (Aβ42) accumulation is increasingly recognized as an early event in the pathogenesis of Alzheimer's disease (AD). We have developed a doxycycline-inducible adenoviral-based system that directs intracellular Aβ42 expression and accumulation into the endoplasmic reticulum of primary neuronal cultures in a regulated manner. Aβ42 exhibited a perinuclear distribution in cell bodies and an association with vesicular compartments. Virally expressed intracellular Aβ42 was toxic to neuronal cultures 24 hr after induction in a dose-dependent manner. Aβ42 expression prompted the rapid induction of stress-inducible Hsp70 protein in neurons, and virally mediated Hsp70 overexpression rescued neurons from the toxic effects of intracellular Aβ accumulation. Together, these results implicate the cellular stress response as a possible modulator of Aβ-induced toxicity in neuronal cultures.Keywords
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