PMID- 34865098
OWN - NLM
STAT- MEDLINE
DCOM- 20220210
LR  - 20220210
IS  - 1554-6578 (Electronic)
IS  - 0022-3069 (Linking)
VI  - 81
IP  - 1
DP  - 2022 Jan 21
TI  - MicroRNA-155-5p Targets SKP2, Activates IKKbeta, Increases Abeta Aggregation, and 
      Aggravates a Mouse Alzheimer Disease Model.
PG  - 16-26
LID - 10.1093/jnen/nlab116 [doi]
AB  - The nuclear factor kappa B (NF-kappaB) pathway and inhibitor of NF-kappaB kinase beta (IKKbeta) 
      are involved in Alzheimer disease (AD) pathogenesis. This study explored the 
      mechanisms underlying IKKbeta-mediated Abeta aggregation and neuron regeneration in 
      APP.PS1 mice. Adenoviral transduction particles were injected into the 
      hippocampal CA1 region of the mice to knock down or inhibit target genes. Morris 
      water maze was performed to evaluate the cognitive function of the mice. Abeta 
      deposition was determined by histological examination. sh-IKKbeta plasmids and 
      microRNA (miR)-155-5p inhibitor were transfected into Abeta1-42-induced N2a cells. 
      The expressions of AD-related proteins were detected by Western blot. The 
      interaction between S-phase kinase-associated protein 2 (SKP2) and IKKbeta was 
      assessed by co-immunoprecipitation. IKKbeta knockdown (KD) and miR-155-5p inhibition 
      ameliorated cognitive impairment, improved neuron regeneration, and attenuated Abeta 
      deposition in APP/PS1 mice. SKP2 KD aggravated cognitive impairment, inhibited 
      neuron regeneration, and promoted Abeta deposition in the mice. SKP2 regulated the 
      stability of IKKbeta protein via ubiquitination. MiR-155-5p regulates Abeta deposition 
      and the expression of Abeta generation-related proteins in N2a cells via targeting 
      SKP2. These results indicate that the miR-155-5p/SKP2/IKKbeta axis was critical for 
      pathogenesis in this AD model and suggest the potential of miR-155-5p as a target 
      for AD treatment.
CI  - (c) 2021 American Association of Neuropathologists, Inc. All rights reserved.
FAU - Wang, Wei
AU  - Wang W
AD  - From the Department of Neurology, The Second Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi Province, China.
FAU - Gu, Xun-Hu
AU  - Gu XH
AD  - From the Department of Neurology, The Second Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi Province, China.
FAU - Li, Min
AU  - Li M
AD  - From the Department of Neurology, The Second Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi Province, China.
FAU - Cheng, Zhi-Juan
AU  - Cheng ZJ
AD  - From the Department of Neurology, The Second Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi Province, China.
FAU - Tian, Sheng
AU  - Tian S
AD  - From the Department of Neurology, The Second Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi Province, China.
FAU - Liao, Ying
AU  - Liao Y
AD  - From the Department of Neurology, The Second Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi Province, China.
FAU - Liu, Xu
AU  - Liu X
AUID- ORCID: 0000-0001-5926-7795
AD  - From the Department of Neurology, The Second Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi Province, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (MIRN155 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn155 microRNA, mouse)
RN  - 0 (S-Phase Kinase-Associated Proteins)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
SB  - IM
MH  - Alzheimer Disease/*pathology
MH  - Animals
MH  - Disease Models, Animal
MH  - HEK293 Cells
MH  - Humans
MH  - I-kappa B Kinase/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/*metabolism
MH  - S-Phase Kinase-Associated Proteins/*metabolism
OTO - NOTNLM
OT  - (IKKbeta)
OT  - Alzheimer disease
OT  - Inhibitor of nuclear factor kappa B kinase beta
OT  - MicroRNA-155-5p
OT  - Nuclear factor kappa B (NF-kappaB)
OT  - S-phase kinase-associated protein 2 (SKP2)
EDAT- 2021/12/06 06:00
MHDA- 2022/02/11 06:00
CRDT- 2021/12/05 21:45
PHST- 2021/12/06 06:00 [pubmed]
PHST- 2022/02/11 06:00 [medline]
PHST- 2021/12/05 21:45 [entrez]
AID - 6448595 [pii]
AID - 10.1093/jnen/nlab116 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 2022 Jan 21;81(1):16-26. doi: 10.1093/jnen/nlab116.