PMID- 29299155
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 66
DP  - 2017 Dec 15
TI  - Neuroprotection by aripiprazole against beta-amyloid-induced toxicity by P-CK2alpha 
      activation via inhibition of GSK-3beta.
PG  - 110380-110391
LID - 10.18632/oncotarget.22777 [doi]
AB  - Psychosis is reported over 30% of patients with Alzheimer's disease (AD) in 
      clinics. Aripiprazole is an atypical antipsychotic drug with partial agonist 
      activity at the D(2) dopamine and 5-HT(1A) receptors with low side-effect 
      profile. We identified aripiprazole is able to overcome the amyloid-beta (Abeta)-evoked 
      neurotoxicity and then increase the cell viability. This study elucidated the 
      mechanism(s) by which aripiprazole ameliorates Abeta1-42-induced decreased neurite 
      outgrowth and viability in neuronal cells. Pretreatment with aripiprazole 
      increased Brain-derived neurotrophic factor (BDNF) mRNA and protein expressions 
      in N2a cells. Additionally, phosphorylated casein kinase 2alpha at Y 255 (P-CK2alpha) was 
      increased in time- and concentration-dependent manners. Furthermore, 
      Abeta1-42-induced decreased BDNF and P-CK2alpha expression were increased over control 
      level by aripiprazole. Subsequently, Abeta1-42-induced decreased levels of 
      phosphorylated glycogen synthase-3beta at Ser9 (P-GSK-3beta) and nuclear P-beta-catenin 
      (Ser675) were elevated by aripiprazole, which were inhibited by K252A (inhibitor 
      of BDNF receptor) and tetrabromocinnamic acid (TBCA, CK2 inhibitor), indicating 
      that BDNF and P-CK2alpha activation are implicated in the aripiprazole effects. 
      Expressions of cyclin D1 and insulin-like growth factor 2 (IGF2) mRNA were 
      increased by aripiprazole; even in the presence of Abeta1-42, which was blocked by 
      K252A and TBCA. In CK2alpha gene-silenced N2a cells, aripiprazole failed to increase 
      P-GSK-3beta and P-beta-catenin expressions. Consequently, aripiprazole ameliorated 
      Abeta1-42-induced attenuation of neurite elongation in HT22 cells, and this effect 
      was blocked by both TBCA and imatinib. Decreased viability induced by Abeta1-42 was 
      recovered by aripiprazole. These findings provide evidence supporting that 
      aripiprazole can provide an effective therapeutic strategy against Abeta-induced 
      neurotoxicity in AD-associated psychosis.
FAU - Park, So Youn
AU  - Park SY
AD  - Department of Pharmacology, School of Medicine, Pusan National University, 
      Gyeongsangnam-do 50612, Republic of Korea.
AD  - Gene & Cell Therapy Research Center for Vessel-associated Diseases, Pusan 
      National University, Gyeongsangnam-do 50612, Republic of Korea.
FAU - Shin, Hwa Kyoung
AU  - Shin HK
AD  - Department of Korean Medical Science, School of Korean Medicine, Pusan National 
      University, Gyeongsangnam-do 50612, Republic of Korea.
FAU - Lee, Won Suk
AU  - Lee WS
AD  - Department of Pharmacology, School of Medicine, Pusan National University, 
      Gyeongsangnam-do 50612, Republic of Korea.
FAU - Bae, Sun Sik
AU  - Bae SS
AD  - Department of Pharmacology, School of Medicine, Pusan National University, 
      Gyeongsangnam-do 50612, Republic of Korea.
AD  - Gene & Cell Therapy Research Center for Vessel-associated Diseases, Pusan 
      National University, Gyeongsangnam-do 50612, Republic of Korea.
FAU - Kim, Koanhoi
AU  - Kim K
AD  - Department of Pharmacology, School of Medicine, Pusan National University, 
      Gyeongsangnam-do 50612, Republic of Korea.
FAU - Hong, Ki Whan
AU  - Hong KW
AD  - Gene & Cell Therapy Research Center for Vessel-associated Diseases, Pusan 
      National University, Gyeongsangnam-do 50612, Republic of Korea.
FAU - Kim, Chi Dae
AU  - Kim CD
AD  - Department of Pharmacology, School of Medicine, Pusan National University, 
      Gyeongsangnam-do 50612, Republic of Korea.
AD  - Gene & Cell Therapy Research Center for Vessel-associated Diseases, Pusan 
      National University, Gyeongsangnam-do 50612, Republic of Korea.
LA  - eng
PT  - Journal Article
DEP - 20171130
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5746390
OTO - NOTNLM
OT  - CK2alpha
OT  - GSK-3beta
OT  - Wnt/beta-catenin pathway
OT  - alzheimer's disease
OT  - aripiprazole
COIS- CONFLICTS OF INTEREST The authors declare no potential conflicts of interest.
EDAT- 2018/01/05 06:00
MHDA- 2018/01/05 06:01
PMCR- 2017/12/15
CRDT- 2018/01/05 06:00
PHST- 2017/05/13 00:00 [received]
PHST- 2017/11/19 00:00 [accepted]
PHST- 2018/01/05 06:00 [entrez]
PHST- 2018/01/05 06:00 [pubmed]
PHST- 2018/01/05 06:01 [medline]
PHST- 2017/12/15 00:00 [pmc-release]
AID - 22777 [pii]
AID - 10.18632/oncotarget.22777 [doi]
PST - epublish
SO  - Oncotarget. 2017 Nov 30;8(66):110380-110391. doi: 10.18632/oncotarget.22777. 
      eCollection 2017 Dec 15.