Extracellular Hsp90α Detoxifies β-Amyloid Fibrils Through an NRF2 and Autophagy Dependent Pathway
Murshid, A.; Lang, B. J.; Borges, T. J.; Okusha, Y.; Doshi, S. P.; Yasmine, S.; Clark-Matott, J.; Choudhury, R.; Ang, L.-H.; Woodbury, M.; Ikezu, T.; Calderwood, S. K.
Show abstract
We have investigated the role of extracellular Heat shock protein 90 alpha (eHsp90) in conferring protection of neuronal cells against fibrillary amyloid beta (f-A{beta}1-42) toxicity mediated by microglial cells. Formation of f-A{beta}1-42 plaques leads to neurotoxic inflammation, a critical pathological feature of Alzheimers Disease. We observed increased uptake and clearance of internalized f-A{beta}1-42 by microglial cells treated with eHsp90, an effect associated with activation of NRF2 (NF-E2-related factor 2) - mediated autophagy. eHsp90 thus mitigated the neuronal toxicity of f-A{beta}1-42-activated microglia. In addition, eHsp90 facilitated f-A{beta}1-42 engulfment by microglial cells in vitro. In summary, eHsp90 triggers NRF2-mediated autophagy in microglia and thus protects against the neurotoxic effects of f-A{beta}1-42.
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