PMID- 31796678
OWN - NLM
STAT- MEDLINE
DCOM- 20201118
LR  - 20211204
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 73
IP  - 2
DP  - 2020
TI  - Carnosic Acid Reverses the Inhibition of ApoE4 on Cell Surface Level of ApoER2 
      and Reelin Signaling Pathway.
PG  - 517-528
LID - 10.3233/JAD-190914 [doi]
AB  - The cell surface level of apolipoprotein E receptor 2 (ApoER2) increases by 
      cyclic transport of ApoER2 and then activates Reelin signaling pathway to exert 
      neuroprotective function in AD. ApoER2 ligand Apolipoprotein E4 (ApoE4) inhibits 
      the recycling of ApoER2 to the cell surface rendering neurons unresponsive to 
      Reelin. Carnosic acid (CA) is proven to possess neuroprotective and neurotrophic 
      functions in Alzheimer's disease (AD) mouse model. However, there are few reports 
      about how ApoE4 impairs the recycling of ApoER2 and if CA can affect the cyclic 
      transport of ApoER2. In this study, we demonstrated that ApoE4 attenuates the 
      binding of sorting nexin 17 (SNX17) to ApoER2 and inhibits the recycling of 
      ApoER2, resulting in decreased cell surface level of ApoER2. Further, we found 
      that CA enhances the binding of SNX17 to ApoER2, counteracts the negative effects 
      of ApoE4 on the cell surface level of ApoER2 to reverse the ApoE4-induced 
      reduction in Reelin signaling activation by increasing the phosphorylation of the 
      N-methyl-D-aspartate receptor (NMDAR) and cAMP-response element-binding protein 
      (CREB) and the expression of Gria2. Thus, CA promotes neurite growth inhibited by 
      ApoE4. Our work suggests that CA may be a potential approach to attenuate the 
      risk of ApoE4-associated AD.
FAU - Feng, Maoxiao
AU  - Feng M
AD  - Department of Human Anatomy and Key Laboratory of Experimental Teratology, 
      Ministry of Education, Shandong University School of Medicine, Jinan, Shandong, 
      China.
FAU - Cui, Donghai
AU  - Cui D
AD  - Department of Human Anatomy and Key Laboratory of Experimental Teratology, 
      Ministry of Education, Shandong University School of Medicine, Jinan, Shandong, 
      China.
FAU - Li, Yi
AU  - Li Y
AD  - Department of Neurology, Qilu Hospital, Shandong University, Jinan, Shandong, 
      China.
FAU - Shi, Jian
AU  - Shi J
AD  - Department of Neurology, Department of Veterans Affairs Medical Center, San 
      Francisco and University of California, San Francisco, CA, USA.
FAU - Xiang, Lan
AU  - Xiang L
AD  - School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China.
FAU - Bian, Hong
AU  - Bian H
AD  - Department of Neurology, Jinan Central Hospital, Shandong University, Jinan, 
      Shandong, China.
FAU - Ma, Zhiyong
AU  - Ma Z
AD  - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese 
      Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong 
      University, Jinan, Shandong, China.
FAU - Xia, Wen
AU  - Xia W
AD  - Department of Neurology, Qilu Hospital, Shandong University, Jinan, Shandong, 
      China.
FAU - Wei, Guangwei
AU  - Wei G
AD  - Department of Human Anatomy and Key Laboratory of Experimental Teratology, 
      Ministry of Education, Shandong University School of Medicine, Jinan, Shandong, 
      China.
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Abietanes)
RN  - 0 (Apolipoprotein E4)
RN  - 0 (Cell Adhesion Molecules, Neuronal)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Low Density Lipoprotein Receptor-Related Protein-1)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Reelin Protein)
RN  - 0 (Reln protein, rat)
RN  - 0 (SNX17 protein, human)
RN  - 0 (Sorting Nexins)
RN  - EC 3.4.21.- (RELN protein, human)
RN  - EC 3.4.21.- (Reln protein, mouse)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - LI791SXT24 (salvin)
RN  - P6W5IXV8V9 (glutamate receptor ionotropic, AMPA 2)
SB  - IM
MH  - Abietanes/*pharmacology
MH  - Animals
MH  - Apolipoprotein E4/*antagonists & inhibitors
MH  - Cell Adhesion Molecules, Neuronal/*metabolism
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Extracellular Matrix Proteins/*metabolism
MH  - Female
MH  - Humans
MH  - Low Density Lipoprotein Receptor-Related Protein-1/*antagonists & 
      inhibitors/metabolism
MH  - Nerve Tissue Proteins/*metabolism
MH  - Neurites/drug effects
MH  - Neuroprotective Agents/*pharmacology
MH  - PC12 Cells
MH  - Pregnancy
MH  - Rats
MH  - Receptors, AMPA/biosynthesis/genetics
MH  - Receptors, Cell Surface/drug effects
MH  - Receptors, N-Methyl-D-Aspartate/drug effects
MH  - Reelin Protein
MH  - Serine Endopeptidases/*metabolism
MH  - Signal Transduction/*drug effects
MH  - Sorting Nexins/metabolism
OTO - NOTNLM
OT  - Apolipoprotein E receptor 2
OT  - Apolipoprotein E4
OT  - Reelin signaling pathway
OT  - carnosic acid
OT  - sorting nexin 17
EDAT- 2019/12/05 06:00
MHDA- 2020/11/20 06:00
CRDT- 2019/12/05 06:00
PHST- 2019/12/05 06:00 [pubmed]
PHST- 2020/11/20 06:00 [medline]
PHST- 2019/12/05 06:00 [entrez]
AID - JAD190914 [pii]
AID - 10.3233/JAD-190914 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2020;73(2):517-528. doi: 10.3233/JAD-190914.