Protection of murine neural progenitor cells by the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin in the low nanomolar concentration range

Guanghu Wang, Kannan Krishnamurthy, Dantera Tangpisuthipongsa

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Stem cell-based approaches provide hope as a potential therapy for neurodegenerative diseases and stroke. One of the major scientific hurdles for stem cell therapy is the poor survival rate of the newly formed or transplanted neural stem cells. In this study, we found that low-dose treatment with the Heat shock protein 90 (Hsp90) inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG), a heavily investigated anti-cancer drug, prevented neural progenitor cells from either naturally-occurring or stress-induced apoptosis, although it induced apoptosis at higher doses. This stress adaptation effect mediated by low-dose 17-AAG is accompanied by activation of multiple cell survival pathways, including the stress response pathway (induction of Hsp70), the MAPK pathway, and the PI3K/Akt pathway. When administered in vivo, 17-AAG led to Akt and glycogen synthase kinase 3β phosphorylation, and more 5-bromo-2â- deoxyuridine positive cells in the mouse brain. These findings could have profound implications in stem cell therapy for neurodegenerative diseases and stroke.

Original languageEnglish (US)
Pages (from-to)703-711
Number of pages9
JournalJournal of Neurochemistry
Volume117
Issue number4
DOIs
StatePublished - May 1 2011

Fingerprint

tanespimycin
HSP90 Heat-Shock Proteins
Stem cells
Stem Cells
Neurodegenerative diseases
Cell- and Tissue-Based Therapy
Neurodegenerative Diseases
Stroke
Cells
Apoptosis
Glycogen Synthase Kinase 3
Phosphorylation
Neural Stem Cells
Bromodeoxyuridine
Phosphatidylinositol 3-Kinases
Brain
Cell Survival
Chemical activation
Neuroprotection
Therapeutics

Keywords

  • 17-AAG
  • hormesis
  • neurodegenerative diseases
  • neuroprogenitor
  • stem cell
  • stress adaptation

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Protection of murine neural progenitor cells by the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin in the low nanomolar concentration range. / Wang, Guanghu; Krishnamurthy, Kannan; Tangpisuthipongsa, Dantera.

In: Journal of Neurochemistry, Vol. 117, No. 4, 01.05.2011, p. 703-711.

Research output: Contribution to journalArticle

@article{3e1c5d48202941a0af8b5cc52f7ee0dc,
title = "Protection of murine neural progenitor cells by the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin in the low nanomolar concentration range",
abstract = "Stem cell-based approaches provide hope as a potential therapy for neurodegenerative diseases and stroke. One of the major scientific hurdles for stem cell therapy is the poor survival rate of the newly formed or transplanted neural stem cells. In this study, we found that low-dose treatment with the Heat shock protein 90 (Hsp90) inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG), a heavily investigated anti-cancer drug, prevented neural progenitor cells from either naturally-occurring or stress-induced apoptosis, although it induced apoptosis at higher doses. This stress adaptation effect mediated by low-dose 17-AAG is accompanied by activation of multiple cell survival pathways, including the stress response pathway (induction of Hsp70), the MAPK pathway, and the PI3K/Akt pathway. When administered in vivo, 17-AAG led to Akt and glycogen synthase kinase 3β phosphorylation, and more 5-bromo-2{\^a}- deoxyuridine positive cells in the mouse brain. These findings could have profound implications in stem cell therapy for neurodegenerative diseases and stroke.",
keywords = "17-AAG, hormesis, neurodegenerative diseases, neuroprogenitor, stem cell, stress adaptation",
author = "Guanghu Wang and Kannan Krishnamurthy and Dantera Tangpisuthipongsa",
year = "2011",
month = "5",
day = "1",
doi = "10.1111/j.1471-4159.2011.07239.x",
language = "English (US)",
volume = "117",
pages = "703--711",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Protection of murine neural progenitor cells by the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin in the low nanomolar concentration range

AU - Wang, Guanghu

AU - Krishnamurthy, Kannan

AU - Tangpisuthipongsa, Dantera

PY - 2011/5/1

Y1 - 2011/5/1

N2 - Stem cell-based approaches provide hope as a potential therapy for neurodegenerative diseases and stroke. One of the major scientific hurdles for stem cell therapy is the poor survival rate of the newly formed or transplanted neural stem cells. In this study, we found that low-dose treatment with the Heat shock protein 90 (Hsp90) inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG), a heavily investigated anti-cancer drug, prevented neural progenitor cells from either naturally-occurring or stress-induced apoptosis, although it induced apoptosis at higher doses. This stress adaptation effect mediated by low-dose 17-AAG is accompanied by activation of multiple cell survival pathways, including the stress response pathway (induction of Hsp70), the MAPK pathway, and the PI3K/Akt pathway. When administered in vivo, 17-AAG led to Akt and glycogen synthase kinase 3β phosphorylation, and more 5-bromo-2â- deoxyuridine positive cells in the mouse brain. These findings could have profound implications in stem cell therapy for neurodegenerative diseases and stroke.

AB - Stem cell-based approaches provide hope as a potential therapy for neurodegenerative diseases and stroke. One of the major scientific hurdles for stem cell therapy is the poor survival rate of the newly formed or transplanted neural stem cells. In this study, we found that low-dose treatment with the Heat shock protein 90 (Hsp90) inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG), a heavily investigated anti-cancer drug, prevented neural progenitor cells from either naturally-occurring or stress-induced apoptosis, although it induced apoptosis at higher doses. This stress adaptation effect mediated by low-dose 17-AAG is accompanied by activation of multiple cell survival pathways, including the stress response pathway (induction of Hsp70), the MAPK pathway, and the PI3K/Akt pathway. When administered in vivo, 17-AAG led to Akt and glycogen synthase kinase 3β phosphorylation, and more 5-bromo-2â- deoxyuridine positive cells in the mouse brain. These findings could have profound implications in stem cell therapy for neurodegenerative diseases and stroke.

KW - 17-AAG

KW - hormesis

KW - neurodegenerative diseases

KW - neuroprogenitor

KW - stem cell

KW - stress adaptation

UR - http://www.scopus.com/inward/record.url?scp=79955019826&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955019826&partnerID=8YFLogxK

U2 - 10.1111/j.1471-4159.2011.07239.x

DO - 10.1111/j.1471-4159.2011.07239.x

M3 - Article

VL - 117

SP - 703

EP - 711

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 4

ER -