PMID- 32377707
OWN - NLM
STAT- MEDLINE
DCOM- 20210210
LR  - 20210927
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 22
IP  - 1
DP  - 2020 Jul
TI  - PNU282987 inhibits amyloid‑beta aggregation by upregulating astrocytic endogenous 
      alphaB‑crystallin and HSP‑70 via regulation of the alpha7AChR, PI3K/Akt/HSF‑1 signaling 
      axis.
PG  - 201-208
LID - 10.3892/mmr.2020.11132 [doi]
AB  - Alzheimer's disease (AD) is a chronic and irreversible neurodegenerative 
      disorder. Abnormal aggregation of the neurotoxic amyloid‑beta (Abeta) peptide is an 
      early event in AD. The activation of astrocytic alpha7 nicotinic acetylcholine 
      receptor (alpha7 nAChR) can inhibit Abeta aggregation; thus, the molecular mechanism 
      between alpha7 nAChR activation and Abeta aggregation warrants further investigation. In 
      the present study, Abeta oligomer levels were assessed in astrocytic cell lysates 
      after treatment with PNU282987 (a potent agonist of alpha7 nAChRs) or co‑treatment 
      with LY294002, a p‑Akt inhibitor. The levels of heat shock factor‑1 (HSF‑1), heat 
      shock protein 70 (HSP‑70), and alphaB‑crystallin (Cryab) in astrocytes treated with 
      PNU282987 at various time‑points or co‑treated with methyllycaconitine (MLA), a 
      selective alpha7 nAChR antagonist, as well as co‑incubated with LY294002 were 
      determined by western blotting. HSP‑70 and Cryab levels were determined after 
      HSF‑1 knockdown (KD) in astrocytes. PNU282987 markedly inhibited Abeta aggregation 
      and upregulated HSF‑1, Cryab, and HSP‑70 in primary astrocytes, while the 
      PNU282987‑mediated neuroprotective effect was reversed by pre‑treatment with MLA 
      or LY294002. Moreover, the HSF‑1 KD in astrocytes effectively decreased Cryab, 
      but not HSP‑70 expression. HSF‑1 is necessary for the upregulation of Cryab 
      expression, but not for that of HSP‑70. HSF‑1 and HSP‑70 have a neuroprotective 
      effect. Furthermore, the neuroprotective effect of PNU282987 against Abeta 
      aggregation was mediated by the canonical PI3K/Akt signaling pathway activation.
FAU - Ren, Zhenkui
AU  - Ren Z
AD  - Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education, College of 
      Basic Medical Sciences, Guiyang, Guizhou 550004, P.R. China.
FAU - Dong, Zhihui
AU  - Dong Z
AD  - Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education, College of 
      Basic Medical Sciences, Guiyang, Guizhou 550004, P.R. China.
FAU - Xie, Peng
AU  - Xie P
AD  - Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education, College of 
      Basic Medical Sciences, Guiyang, Guizhou 550004, P.R. China.
FAU - Lv, Ju
AU  - Lv J
AD  - Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education, College of 
      Basic Medical Sciences, Guiyang, Guizhou 550004, P.R. China.
FAU - Hu, Yumei
AU  - Hu Y
AD  - Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education, College of 
      Basic Medical Sciences, Guiyang, Guizhou 550004, P.R. China.
FAU - Guan, Zhizhong
AU  - Guan Z
AD  - Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education, College of 
      Basic Medical Sciences, Guiyang, Guizhou 550004, P.R. China.
FAU - Zhang, Chunlin
AU  - Zhang C
AD  - College of Basic Medical Sciences, Guizhou Medical University, Guiyang, Guizhou 
      550025, P.R. China.
FAU - Yu, Wenfeng
AU  - Yu W
AD  - Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education, College of 
      Basic Medical Sciences, Guiyang, Guizhou 550004, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20200505
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Benzamides)
RN  - 0 (Bridged Bicyclo Compounds)
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (Nicotinic Agonists)
RN  - 0 (PNU-282987)
RN  - 0 (Protein Aggregates)
RN  - 0 (alpha-Crystallins)
RN  - 0 (alpha7 Nicotinic Acetylcholine Receptor)
RN  - 0 (beta-Crystallins)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Amyloid beta-Peptides/*metabolism
MH  - Animals
MH  - Astrocytes/*drug effects/metabolism
MH  - Benzamides/*pharmacology
MH  - Bridged Bicyclo Compounds/*pharmacology
MH  - Cells, Cultured
MH  - Female
MH  - HSP70 Heat-Shock Proteins/metabolism
MH  - Male
MH  - Nicotinic Agonists/*pharmacology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Protein Aggregates/drug effects
MH  - Protein Aggregation, Pathological/metabolism/*prevention & control
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/*drug effects
MH  - Up-Regulation/drug effects
MH  - alpha-Crystallins/metabolism
MH  - alpha7 Nicotinic Acetylcholine Receptor/agonists/metabolism
MH  - beta-Crystallins/metabolism
PMC - PMC7248489
OTO - NOTNLM
OT  - alphaB-crystallin
OT  - alzheimer's disease
OT  - neuroprotection
OT  - Pi3K/akt
OT  - astrocyte
OT  - HSP-70
OT  - HSF-1
OT  - Pnu282987
EDAT- 2020/05/08 06:00
MHDA- 2021/02/11 06:00
PMCR- 2020/05/05
CRDT- 2020/05/08 06:00
PHST- 2019/12/04 00:00 [received]
PHST- 2020/03/23 00:00 [accepted]
PHST- 2020/05/08 06:00 [pubmed]
PHST- 2021/02/11 06:00 [medline]
PHST- 2020/05/08 06:00 [entrez]
PHST- 2020/05/05 00:00 [pmc-release]
AID - MMR-22-01-0201 [pii]
AID - 10.3892/mmr.2020.11132 [doi]
PST - ppublish
SO  - Mol Med Rep. 2020 Jul;22(1):201-208. doi: 10.3892/mmr.2020.11132. Epub 2020 May 
      5.