PMID- 23593505
OWN - NLM
STAT- MEDLINE
DCOM- 20131022
LR  - 20220309
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 4
DP  - 2013
TI  - Fingolimod phosphate attenuates oligomeric amyloid beta-induced neurotoxicity via 
      increased brain-derived neurotrophic factor expression in neurons.
PG  - e61988
LID - 10.1371/journal.pone.0061988 [doi]
LID - e61988
AB  - The neurodegenerative processes that underlie Alzheimer's disease are mediated, 
      in part, by soluble oligomeric amyloid beta, a neurotoxic protein that inhibits 
      hippocampal long-term potentiation, disrupts synaptic plasticity, and induces the 
      production of reactive oxygen species. Here we show that the 
      sphingosine-1-phosphate (S1P) receptor (S1PR) agonist fingolimod phosphate 
      (FTY720-P)-a new oral drug for multiple sclerosis-protects neurons against 
      oligomeric amyloid beta-induced neurotoxicity. We confirmed that primary mouse 
      cortical neurons express all of the S1P receptor subtypes and FTY720-P directly 
      affects the neurons. Treatment with FTY720-P enhanced the expression of 
      brain-derived neurotrophic factor (BDNF) in neurons. Moreover, blocking BDNF-TrkB 
      signaling with a BDNF scavenger, TrkB inhibitor, or ERK1/2 inhibitor almost 
      completely ablated these neuroprotective effects. These results suggested that 
      the neuroprotective effects of FTY720-P are mediated by upregulated neuronal BDNF 
      levels. Therefore, FTY720-P may be a promising therapeutic agent for 
      neurodegenerative diseases, such as Alzheimer's disease.
FAU - Doi, Yukiko
AU  - Doi Y
AD  - Department of Neuroimmunology, Research Institute of Environmental Medicine, 
      Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan.
FAU - Takeuchi, Hideyuki
AU  - Takeuchi H
FAU - Horiuchi, Hiroshi
AU  - Horiuchi H
FAU - Hanyu, Taketo
AU  - Hanyu T
FAU - Kawanokuchi, Jun
AU  - Kawanokuchi J
FAU - Jin, Shijie
AU  - Jin S
FAU - Parajuli, Bijay
AU  - Parajuli B
FAU - Sonobe, Yoshifumi
AU  - Sonobe Y
FAU - Mizuno, Tetsuya
AU  - Mizuno T
FAU - Suzumura, Akio
AU  - Suzumura A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130412
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (FTY 720P)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Neurotoxins)
RN  - 0 (Organophosphates)
RN  - 0 (Receptors, Lysosphingolipid)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - NGZ37HRE42 (Sphingosine)
SB  - IM
MH  - Amyloid beta-Peptides/*toxicity
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/biosynthesis/*metabolism
MH  - Cytoprotection/drug effects
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Humans
MH  - MAP Kinase Signaling System/drug effects
MH  - Mice
MH  - Neurons/drug effects/enzymology/*metabolism/*pathology
MH  - Neuroprotective Agents/pharmacology
MH  - Neurotoxins/*toxicity
MH  - Organophosphates/*pharmacology
MH  - Protein Multimerization/*drug effects
MH  - Receptor, trkB/metabolism
MH  - Receptors, Lysosphingolipid/metabolism
MH  - Sphingosine/*analogs & derivatives/pharmacology
PMC - PMC3625222
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/04/18 06:00
MHDA- 2013/10/23 06:00
PMCR- 2013/04/12
CRDT- 2013/04/18 06:00
PHST- 2012/12/03 00:00 [received]
PHST- 2013/03/17 00:00 [accepted]
PHST- 2013/04/18 06:00 [entrez]
PHST- 2013/04/18 06:00 [pubmed]
PHST- 2013/10/23 06:00 [medline]
PHST- 2013/04/12 00:00 [pmc-release]
AID - PONE-D-12-38422 [pii]
AID - 10.1371/journal.pone.0061988 [doi]
PST - epublish
SO  - PLoS One. 2013 Apr 12;8(4):e61988. doi: 10.1371/journal.pone.0061988. Print 2013.