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
Y1 - 2011/5
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
C2 - 21395580
AN - SCOPUS:79955019826
SN - 0022-3042
VL - 117
SP - 703
EP - 711
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 4
ER -