Extracellular Hsp90 and protection of neuronal cells through Nrf2

Stuart K. Calderwood, Thiago J. Borges, Takanori Eguchi, Benjamin J. Lang, Ayesha Murshid, Yuka Okusya, Thomas L. Prince

Research output: Contribution to journalReview articlepeer-review

Abstract

Heat shock protein 90 (Hsp90), although one of the most essential intracellular chaperones, can also play key roles in the extracellular milieu. Here, we review the properties of extracellular Hsp90 in cellular homeostasis in the heat shock response (HSR), focusing on cells of the central nervous system. Hsp90 can be secreted by microglia as well as other cell types by non-canonical pathways of secretion. The chaperone may then influence the behavior of distant cells and can for instance protect neuronal cells from the oxidative burst accompanying phagocytosis by microglia of beta-amyloid fibrils. A mechanism involving activation of the transcription factor Nrf2, and induction of the antioxidant response is reported. We review the potential role of extracellular Hsp90, Nrf2 and transcellular chaperone signaling in the non-cell-intrinsic HSR.

Original languageEnglish
Pages (from-to)2299-2306
Number of pages8
JournalBiochemical Society Transactions
Volume49
Issue number5
DOIs
Publication statusPublished - Nov 2021
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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