PMID- 33070839
OWN - NLM
STAT- MEDLINE
DCOM- 20201102
LR  - 20201102
IS  - 1347-8648 (Electronic)
IS  - 1347-8613 (Linking)
VI  - 144
IP  - 4
DP  - 2020 Dec
TI  - Survival motor neuron protein regulates oxidative stress and inflammatory 
      response in microglia of the spinal cord in spinal muscular atrophy.
PG  - 204-211
LID - S1347-8613(20)30090-6 [pii]
LID - 10.1016/j.jphs.2020.09.001 [doi]
AB  - The deficiency of survival motor neuron (SMN) protein can result in the onset of 
      spinal muscular atrophy (SMA), an autosomal recessive disorder characterized by a 
      progressive loss of motor neurons and skeletal muscle atrophy. The mechanism 
      underlying SMA pathology remains unclear. Here, we demonstrate that SMN protein 
      regulates oxidative stress and inflammatory response in microglia. Antisense 
      oligonucleotide, which increases SMN protein expression (SMN-ASO), attenuated SMA 
      model mice phenotypes and suppressed the activation of microglia in the spinal 
      cord. The expression of oxidative stress marker in microglia was decreased by 
      SMN-ASO injection in SMA model mice. Increased reactive oxygen species production 
      and subsequent antioxidative stress reaction was observed in SMN protein-depleted 
      RAW264.7. Furthermore, nuclear factor kappa B (NFkappaB) and c-Jun amino terminal 
      kinase (JNK) signaling, which mainly mediate the inflammatory response, are 
      activated in SMN protein-depleted RAW264.7. Tumor necrosis factor-alpha (TNF-alpha) 
      production is also increased in SMN protein-depleted RAW264.7. These findings 
      suggest that SMN protein regulates oxidative stress and inflammatory response in 
      microglia, supporting current claims that microglia can be an effective target 
      for SMA therapy.
CI  - Copyright (c) 2020 The Authors. Production and hosting by Elsevier B.V. All rights 
      reserved.
FAU - Ando, Shiori
AU  - Ando S
AD  - Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu 
      Pharmaceutical University, Gifu, Japan.
FAU - Osanai, Daiki
AU  - Osanai D
AD  - Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu 
      Pharmaceutical University, Gifu, Japan.
FAU - Takahashi, Kei
AU  - Takahashi K
AD  - Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu 
      Pharmaceutical University, Gifu, Japan.
FAU - Nakamura, Shinsuke
AU  - Nakamura S
AD  - Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu 
      Pharmaceutical University, Gifu, Japan. Electronic address: 
      nakamuras@gifu-pu.ac.jp.
FAU - Shimazawa, Masamitsu
AU  - Shimazawa M
AD  - Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu 
      Pharmaceutical University, Gifu, Japan.
FAU - Hara, Hideaki
AU  - Hara H
AD  - Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu 
      Pharmaceutical University, Gifu, Japan.
LA  - eng
PT  - Journal Article
DEP - 20200910
PL  - Japan
TA  - J Pharmacol Sci
JT  - Journal of pharmacological sciences
JID - 101167001
RN  - 0 (NF-kappa B)
RN  - 0 (Oligonucleotides)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Smn1 protein, mouse)
RN  - 0 (Survival of Motor Neuron 1 Protein)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 5Z9SP3X666 (nusinersen)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Gene Expression/drug effects
MH  - Inflammation/*genetics
MH  - MAP Kinase Signaling System/drug effects
MH  - Mice
MH  - Mice, Transgenic
MH  - Microglia/*metabolism
MH  - Molecular Targeted Therapy
MH  - Muscular Atrophy, Spinal/*drug therapy/*genetics/metabolism
MH  - NF-kappa B/metabolism
MH  - Oligonucleotides/*pharmacology/*therapeutic use
MH  - Oligonucleotides, Antisense/*pharmacology/*therapeutic use
MH  - Oxidative Stress/*genetics
MH  - RAW 264.7 Cells
MH  - Spinal Cord/*cytology
MH  - Survival of Motor Neuron 1 Protein/genetics/*metabolism/*physiology
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - Antisense oligonucleotide
OT  - Macrophage cell
OT  - ROS production
OT  - Righting reflex
OT  - SMA model mouse
COIS- Declaration of Competing Interest The authors have no conflicts of interest.
EDAT- 2020/10/20 06:00
MHDA- 2020/11/03 06:00
CRDT- 2020/10/19 05:25
PHST- 2020/06/25 00:00 [received]
PHST- 2020/08/27 00:00 [revised]
PHST- 2020/09/02 00:00 [accepted]
PHST- 2020/10/19 05:25 [entrez]
PHST- 2020/10/20 06:00 [pubmed]
PHST- 2020/11/03 06:00 [medline]
AID - S1347-8613(20)30090-6 [pii]
AID - 10.1016/j.jphs.2020.09.001 [doi]
PST - ppublish
SO  - J Pharmacol Sci. 2020 Dec;144(4):204-211. doi: 10.1016/j.jphs.2020.09.001. Epub 
      2020 Sep 10.