PMID- 30189266
OWN - NLM
STAT- MEDLINE
DCOM- 20200214
LR  - 20210109
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 133
DP  - 2019 Mar
TI  - Circadian control of BDNF-mediated Nrf2 activation in astrocytes protects 
      dopaminergic neurons from ferroptosis.
PG  - 169-178
LID - S0891-5849(18)31523-5 [pii]
LID - 10.1016/j.freeradbiomed.2018.09.002 [doi]
AB  - Astrocyte-neuron interactions protect neurons from iron-mediated toxicity. As 
      dopamine can be metabolized to reactive quinones, dopaminergic neurons are 
      susceptible to oxidative damage and ferroptosis-like induced cell death. 
      Detoxification enzymes are required to protect neurons. Brain-derived 
      neurotrophic factor (BDNF) plays a key role in the regulation of redox sensitive 
      transcription factor Nrf2 in astrocytes and metabolic cooperation between 
      astrocytes and neurons. This article reviews the importance of BDNF and 
      astrocyte-neuron interactions in the protection of neurons against oxidative 
      damages in rodent brains. We previously proposed that BDNF activates Nrf2 via the 
      truncated TrkB.T1 and p75(NTR) receptor complex in astrocytes. Stimulation by 
      BDNF generates the signaling molecule ceramide, which activates PKCzeta leading to 
      induction of the CK2-Nrf2 signaling axis. As a cell clock regulates p75(NTR) 
      expression, we suggested that BDNF effectively activates Nrf2 in astrocytes 
      during the rest phase. In contrast, neurons express both TrkB.FL and TrkB.T1, and 
      TrkB.FL tyrosine kinase activity inhibits p75(NTR)-dependent ceramide generation 
      and internalizes p75(NTR). Therefore, BDNF may not effectively activate Nrf2 in 
      neurons. Notably, neurons only weakly activate detoxification and antioxidant 
      enzymes/proteins via the Nrf2-ARE signaling axis. Thus, astrocytes may provide 
      relevant transcripts and/or proteins to neurons via microparticles/exosomes 
      increasing neuronal resistance to oxidative stress. Circadian increases in the 
      levels of circulating glucocorticoids may further facilitate material transfer 
      from astrocytes to neurons via the stimulation of pannexin 1 channels-P2X7R 
      signaling pathway in astrocytes at the beginning of the active phase. 
      Dysregulation of astrocyte-neuron interactions could therefore contribute to the 
      pathogenesis of neurodegenerative diseases including Parkinson's disease.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Ishii, Tetsuro
AU  - Ishii T
AD  - School of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan. 
      Electronic address: ishiitetsuro305@gmail.com.
FAU - Warabi, Eiji
AU  - Warabi E
AD  - School of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan.
FAU - Mann, Giovanni E
AU  - Mann GE
AD  - School of Cardiovascular Medicine and Sciences, King's British Heart Foundation 
      Centre of Research Excellence, Faculty of Life Sciences and Medicine, King's 
      College London, London SE1 9NH, UK.
LA  - eng
GR  - FS/15/6/31298/BHF_/British Heart Foundation/United Kingdom
GR  - FS/16/67/32548/BHF_/British Heart Foundation/United Kingdom
GR  - MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20180904
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, mouse)
RN  - E1UOL152H7 (Iron)
RN  - EC 2.7.10.1 (Ntrk2 protein, mouse)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - Astrocytes/metabolism
MH  - Brain-Derived Neurotrophic Factor/*genetics/metabolism
MH  - Circadian Clocks/genetics
MH  - Dopaminergic Neurons/*metabolism
MH  - Ferroptosis/genetics
MH  - Iron/*metabolism
MH  - Membrane Glycoproteins/genetics/metabolism
MH  - Mice
MH  - NF-E2-Related Factor 2/*genetics/metabolism
MH  - Oxidative Stress/genetics
MH  - Parkinson Disease/genetics/metabolism/pathology
MH  - Protein-Tyrosine Kinases/genetics/metabolism
MH  - Rats
MH  - Rodentia
OTO - NOTNLM
OT  - BDNF
OT  - CK2
OT  - Circadian rhythm
OT  - Cystine transport
OT  - Dopamine
OT  - Ferroptosis
OT  - GSH
OT  - Mitochondria
OT  - Nrf2
OT  - PKA
OT  - Parkinson's disease
OT  - TrkB
OT  - p75(NTR)
EDAT- 2018/09/07 06:00
MHDA- 2020/02/15 06:00
CRDT- 2018/09/07 06:00
PHST- 2018/07/09 00:00 [received]
PHST- 2018/08/20 00:00 [revised]
PHST- 2018/09/01 00:00 [accepted]
PHST- 2018/09/07 06:00 [pubmed]
PHST- 2020/02/15 06:00 [medline]
PHST- 2018/09/07 06:00 [entrez]
AID - S0891-5849(18)31523-5 [pii]
AID - 10.1016/j.freeradbiomed.2018.09.002 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2019 Mar;133:169-178. doi: 
      10.1016/j.freeradbiomed.2018.09.002. Epub 2018 Sep 4.