PMID- 25596147
OWN - NLM
STAT- MEDLINE
DCOM- 20160414
LR  - 20211203
IS  - 1590-3478 (Electronic)
IS  - 1590-1874 (Linking)
VI  - 36
IP  - 7
DP  - 2015 Jul
TI  - Wogonin increases beta-amyloid clearance and inhibits tau phosphorylation via 
      inhibition of mammalian target of rapamycin: potential drug to treat Alzheimer's 
      disease.
PG  - 1181-8
LID - 10.1007/s10072-015-2070-z [doi]
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Many 
      molecular lesions have been detected in AD, of which the most commonly observed 
      is the accumulation of misfolded proteins, including beta-amyloid (Abeta40 and Abeta42) 
      and tau, in the aging brain. The mammalian target of rapamycin (mTOR) pathway 
      mediates Abeta clearance through autophagy and regulates tau phosphorylation via 
      glycogen synthase kinase-3beta (GSK3beta). Thus, mTOR becomes an important therapeutic 
      target for AD. However, no mTOR inhibitor has yet been marketed to treat AD. 
      Here, we discovered a natural product, wogonin, which could potently promote Abeta 
      clearance in the primary neural astrocytes and significantly decrease Abeta 
      secretion in SH-SY5Y-APP and BACE1 cells [SH-SY5Y cells stably expressing the 
      human amyloid precursor protein (APP) and beta-secretase (BACE1)] through the 
      mTOR/autophagy signaling pathway. Additionally, further research revealed that 
      wogonin inhibited the activity of GSK3beta via mTOR inhibition, finally leading to 
      tau phosphorylation reduction in SH-SHY5Y cells and primary neural astrocytes. In 
      conclusion, our study identified a small molecule, wogonin, which could 
      effectively promote Abeta clearance and decrease tau phosphorylation, and 
      highlighted its therapeutic potential for AD treatment.
FAU - Zhu, Yuyou
AU  - Zhu Y
AD  - Department of Neurology, Anhui Provincial Hospital Affiliated to Anhui Medical 
      University, Hefei, 230001, China, horror2001@sina.com.
FAU - Wang, Juan
AU  - Wang J
LA  - eng
PT  - Journal Article
DEP - 20150118
PL  - Italy
TA  - Neurol Sci
JT  - Neurological sciences : official journal of the Italian Neurological Society and 
      of the Italian Society of Clinical Neurophysiology
JID - 100959175
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Flavanones)
RN  - 0 (Peptide Fragments)
RN  - 0 (amyloid beta-protein (1-40))
RN  - 0 (tau Proteins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (GSK3B protein, human)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - POK93PO28W (wogonin)
SB  - IM
MH  - Amyloid beta-Peptides/*metabolism
MH  - Animals
MH  - Astrocytes/drug effects/metabolism
MH  - Autophagy/*drug effects
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Embryo, Mammalian
MH  - Flavanones/*pharmacology
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Humans
MH  - Microscopy, Confocal
MH  - Neuroblastoma/pathology
MH  - Peptide Fragments/*metabolism
MH  - Phosphorylation/drug effects
MH  - Signal Transduction/*drug effects/physiology
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Transfection
MH  - tau Proteins/*metabolism
EDAT- 2015/01/18 06:00
MHDA- 2016/04/15 06:00
CRDT- 2015/01/18 06:00
PHST- 2014/05/26 00:00 [received]
PHST- 2015/01/08 00:00 [accepted]
PHST- 2015/01/18 06:00 [entrez]
PHST- 2015/01/18 06:00 [pubmed]
PHST- 2016/04/15 06:00 [medline]
AID - 10.1007/s10072-015-2070-z [doi]
PST - ppublish
SO  - Neurol Sci. 2015 Jul;36(7):1181-8. doi: 10.1007/s10072-015-2070-z. Epub 2015 Jan 
      18.