TY - JOUR
T1 - Diosgenin restores Aβ-induced axonal degeneration by reducing the expression of heat shock cognate 70 (HSC70)
AU - Yang, Ximeng
AU - Tohda, Chihiro
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - We previously found diosgenin, an herbal drug-derived steroid sapogenin, to be remarkably effective at restoring Aβ-induced axonal degeneration and improving memory function in model of Alzheimer’s disease (AD), 5XFAD mouse. In this study, we investigated the downstream signaling of diosgenin and explored new therapeutic targets in AD. We showed that the expression of heat shock cognate (HSC) 70 was increased in Aβ-treated neurons and in 5XFAD mice but was decreased by diosgenin treatment. In addition, knockdown of HSC70 significantly promoted axonal growth in neurons. As an association molecule of HSC70 in neurons, α-tubulin was detected by immunoprecipitation. After Aβ treatment, α-tubulin expression was greatly reduced in the degenerated axons, suggesting that a decline in α-tubulin may be one of the factors which correlates with axonal disruption in AD pathology. We hypothesized that the degradation of α-tubulin is triggered by the chaperone activity of HSC70. However, diosgenin significantly normalized the α-tubulin level, a potentially critical process for axonal formation. Our study indicated that reducing the HSC70 level is a new possible therapeutic target of axonal regeneration in AD.
AB - We previously found diosgenin, an herbal drug-derived steroid sapogenin, to be remarkably effective at restoring Aβ-induced axonal degeneration and improving memory function in model of Alzheimer’s disease (AD), 5XFAD mouse. In this study, we investigated the downstream signaling of diosgenin and explored new therapeutic targets in AD. We showed that the expression of heat shock cognate (HSC) 70 was increased in Aβ-treated neurons and in 5XFAD mice but was decreased by diosgenin treatment. In addition, knockdown of HSC70 significantly promoted axonal growth in neurons. As an association molecule of HSC70 in neurons, α-tubulin was detected by immunoprecipitation. After Aβ treatment, α-tubulin expression was greatly reduced in the degenerated axons, suggesting that a decline in α-tubulin may be one of the factors which correlates with axonal disruption in AD pathology. We hypothesized that the degradation of α-tubulin is triggered by the chaperone activity of HSC70. However, diosgenin significantly normalized the α-tubulin level, a potentially critical process for axonal formation. Our study indicated that reducing the HSC70 level is a new possible therapeutic target of axonal regeneration in AD.
UR - http://www.scopus.com/inward/record.url?scp=85052204386&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-30102-8
DO - 10.1038/s41598-018-30102-8
M3 - 学術論文
C2 - 30076345
AN - SCOPUS:85052204386
SN - 2045-2322
VL - 8
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 11707
ER -