PMID- 31182681
OWN - NLM
STAT- MEDLINE
DCOM- 20200713
LR  - 20200713
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 11
IP  - 11
DP  - 2019 Jun 10
TI  - Kainic acid Induces production and aggregation of amyloid beta-protein and memory 
      deficits by activating inflammasomes in NLRP3- and NF-kappaB-stimulated pathways.
PG  - 3795-3810
LID - 10.18632/aging.102017 [doi]
AB  - Kainic acid (KA) treatment causes neuronal degeneration, which is a feature of 
      Alzheimer's disease (AD) symptoms such as amyloid beta-protein production and memory 
      deficits. Inflammasomes are known to be critical for the progression of AD. 
      However, the underlying mechanism by which inflammasomes influence AD progression 
      remains unknown. The present study investigated the damaging effect of KA on 
      neurons by focusing on the inflammasome-mediated signaling pathways. Assessments 
      using cultured microglia and mouse brains demonstrated that KA treatment 
      specifically induced inflammasome activation. Mechanistic evaluations showed that 
      KA activated two major components of inflammasomes, nucleotide binding 
      oligomerization domain (NOD)-like receptor (NLR) protein 3 (NLRP3) and nuclear 
      factor (NF)-kappaB, which resulted in the production of interleukin-1beta (IL-1beta) and 
      brain-derived neurotrophic factor (BDNF). Inhibition of NLRP3 or NF-kappaB by 
      Bay11-7082 caused a reduction in the KA-induced expression of interleukin (IL)-1beta 
      and BDNF. Moreover, knockdown of the expression of KA receptors (KARs) such as 
      Grik1 and Grik3 induced suppression of NLRP3 and NF-kappaB, suggesting that KARs 
      function upstream of NLRP3 and NF-kappaB to mediate the effects of KA on regulation 
      of IL-1beta and BDNF expression. Notably, IL-1beta was shown to exert positive effects 
      on the expression of BACE1, which is blocked by Bay11-7082. Overall, our results 
      revealed that Bay11-7082 acts against KA-induced neuronal degeneration, amyloid 
      beta-protein (Abeta) deposition, and memory defects via inflammasomes and further 
      highlighted the protective role of Bay11-7082 in KA-induced neuronal defects.
FAU - Ruan, Yang
AU  - Ruan Y
AD  - Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical 
      Sciences, Jilin University, Changchun 130021, China.
FAU - Qiu, Xiang
AU  - Qiu X
AD  - Department of Radiology, The First Hospital of Jilin University, Changchun 
      130021, China.
FAU - Lv, Yu-Dan
AU  - Lv YD
AD  - Department of Neurology and Neuroscience Center, The First Hospital of Jilin 
      University, Changchun 130021, China.
FAU - Dong, Dong
AU  - Dong D
AD  - Department of Radiology, The First Hospital of Jilin University, Changchun 
      130021, China.
FAU - Wu, Xiu-Juan
AU  - Wu XJ
AD  - Department of Neurology and Neuroscience Center, The First Hospital of Jilin 
      University, Changchun 130021, China.
FAU - Zhu, Jie
AU  - Zhu J
AD  - Department of Neurology and Neuroscience Center, The First Hospital of Jilin 
      University, Changchun 130021, China.
AD  - , Department of Neurobiology, Care Sciences and Society, Karolinska Institute, 
      Stockholm 141 86, Sweden.
FAU - Zheng, Xiang-Yu
AU  - Zheng XY
AD  - Department of Neurology and Neuroscience Center, The First Hospital of Jilin 
      University, Changchun 130021, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Inflammasomes)
RN  - 0 (NF-kappa B)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Protein Aggregates)
RN  - 0 (Reactive Oxygen Species)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - Amyloid beta-Peptides/*metabolism
MH  - Animals
MH  - Inflammasomes/*drug effects/metabolism
MH  - Kainic Acid/*pharmacology
MH  - Memory Disorders/*metabolism
MH  - Mice
MH  - Microglia/drug effects/metabolism
MH  - NF-kappa B/*metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism
MH  - Neurons/drug effects/metabolism
MH  - Protein Aggregates/*drug effects
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/drug effects
PMC - PMC6594814
OTO - NOTNLM
OT  - NF-kappaB
OT  - NLRP3
OT  - brain-derived neurotrophic factor
OT  - interleukin-1beta
OT  - kainic acid
COIS- CONFLICTS OF INTEREST: The authors declare no conflicts of interest.
EDAT- 2019/06/12 06:00
MHDA- 2020/07/14 06:00
PMCR- 2019/06/15
CRDT- 2019/06/12 06:00
PHST- 2019/02/01 00:00 [received]
PHST- 2019/06/03 00:00 [accepted]
PHST- 2019/06/12 06:00 [pubmed]
PHST- 2020/07/14 06:00 [medline]
PHST- 2019/06/12 06:00 [entrez]
PHST- 2019/06/15 00:00 [pmc-release]
AID - 102017 [pii]
AID - 10.18632/aging.102017 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2019 Jun 10;11(11):3795-3810. doi: 10.18632/aging.102017.