PMID- 30689566
OWN - NLM
STAT- In-Data-Review
LR  - 20190129
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 67
IP  - 2
DP  - 2019
TI  - Indole Compound NC009-1 Augments APOE and TRKA in Alzheimer's Disease Cell and
      Mouse Models for Neuroprotection and Cognitive Improvement.
PG  - 737-756
LID - 10.3233/JAD-180643 [doi]
AB  - Alzheimer's disease (AD), associated with abnormal accumulation of amyloid-beta
      (Abeta), is the most common cause of dementia among older people. A few studies
      have identified substantial AD biomarkers in blood but their results were
      inconsistent. Here we screened gene expression alterations on Abeta-GFP SH-SY5Y
      neuronal model for AD, and evaluated the findings on peripheral leukocytes from
      78 patients with AD and 56 healthy controls. The therapeutic responses of
      identified biomarker candidates were further examined in Abeta-GFP SH-SY5Y
      neuronal and APP/PS1/Tau triple transgenic (3xTg-AD) mouse models. Downregulation
      of apolipoprotein E (APOE) and tropomyosin receptor kinase A (TRKA) were detected
      in Abeta-GFP SH-SY5Y cells and validated by peripheral leukocytes from AD
      patients. Treatment with an in-house indole compound NC009-1 upregulated the
      expression of APOE and TRKA accompanied with improvement of neurite outgrowth in 
      Abeta-GFP SH-SY5Y cells. NC009-1 further rescued the downregulated APOE and TRKA 
      and reduced Abeta and tau levels in hippocampus and cortex, and ameliorated
      cognitive deficits in streptozocin-induced hyperglycemic 3xTg-AD mice. These
      results suggest the role of APOE and TRKA as potential peripheral biomarkers in
      AD, and offer a new drug development target of AD treatment. Further studies of a
      large series of AD patients will be warranted to verify the findings and confirm 
      the correlation between these markers and therapeutic efficacy.
FAU - Chen, Yi-Chun
AU  - Chen YC
AD  - Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University
      College of Medicine, Taoyuan, Taiwan.
FAU - Chiu, Ya-Jen
AU  - Chiu YJ
AD  - Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
FAU - Lin, Chih-Hsin
AU  - Lin CH
AD  - Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University
      College of Medicine, Taoyuan, Taiwan.
FAU - Hsu, Wen-Chuin
AU  - Hsu WC
AD  - Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University
      College of Medicine, Taoyuan, Taiwan.
AD  - Dementia Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
FAU - Wu, Jia-Lu
AU  - Wu JL
AD  - Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
FAU - Huang, Chen-Hsiang
AU  - Huang CH
AD  - Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
FAU - Lin, Chia-Wei
AU  - Lin CW
AD  - Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
FAU - Yao, Ching-Fa
AU  - Yao CF
AD  - Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan.
FAU - Huang, Hei-Jen
AU  - Huang HJ
AD  - Department of Nursing, Mackay Junior College of Medicine, Nursing and Management,
      Taipei, Taiwan.
FAU - Lo, Yen-Shi
AU  - Lo YS
AD  - Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University
      College of Medicine, Taoyuan, Taiwan.
FAU - Chen, Chiung-Mei
AU  - Chen CM
AD  - Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University
      College of Medicine, Taoyuan, Taiwan.
FAU - Wu, Yih-Ru
AU  - Wu YR
AD  - Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University
      College of Medicine, Taoyuan, Taiwan.
FAU - Chang, Kuo-Hsuan
AU  - Chang KH
AD  - Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University
      College of Medicine, Taoyuan, Taiwan.
FAU - Lee-Chen, Guey-Jen
AU  - Lee-Chen GJ
AD  - Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
FAU - Mei Hsieh-Li, Hsiu
AU  - Mei Hsieh-Li H
AD  - Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
OTO - NOTNLM
OT  - APOE
OT  - Alzheimer's disease
OT  - TRKA
OT  - amyloid-beta
OT  - biomarker
OT  - indole compound
EDAT- 2019/01/29 06:00
MHDA- 2019/01/29 06:00
CRDT- 2019/01/29 06:00
PHST- 2019/01/29 06:00 [pubmed]
PHST- 2019/01/29 06:00 [medline]
PHST- 2019/01/29 06:00 [entrez]
AID - JAD180643 [pii]
AID - 10.3233/JAD-180643 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2019;67(2):737-756. doi: 10.3233/JAD-180643.