PMID- 20463406
OWN - NLM
STAT- MEDLINE
DCOM- 20100913
LR  - 20220408
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Print)
IS  - 1387-2877 (Linking)
VI  - 20 Suppl 2
IP  - Suppl 2
DP  - 2010
TI  - Mitochondria-targeted antioxidants protect against amyloid-beta toxicity in 
      Alzheimer's disease neurons.
PG  - S609-31
LID - 10.3233/JAD-2010-100564 [doi]
AB  - The purpose of our study was to investigate the effects of the 
      mitochondria-targeted antioxidants, MitoQ and SS31, and the anti-aging agent 
      resveratrol on neurons from a mouse model (Tg2576 line) of Alzheimer's disease 
      (AD) and on mouse neuroblastoma (N2a) cells incubated with the amyloid-beta 
      (Abeta) peptide. Using electron and confocal microscopy, gene expression 
      analysis, and biochemical methods, we studied mitochondrial structure and 
      function and neurite outgrowth in N2a cells treated with MitoQ, SS31, and 
      resveratrol, and then incubated with Abeta. In N2a cells only incubated with the 
      Abeta, we found increased expressions of mitochondrial fission genes and 
      decreased expression of fusion genes and also decreased expression of 
      peroxiredoxins. Electron microscopy of the N2a cells incubated with Abeta 
      revealed a significantly increased number of mitochondria, indicating that Abeta 
      fragments mitochondria. Biochemical analysis revealed that function is defective 
      in mitochondria. Neurite outgrowth was significantly decreased in Abeta-incubated 
      N2a cells, indicating that Abeta affects neurite outgrowth. However, in N2a cells 
      treated with MitoQ, SS31, and resveratrol, and then incubated with Abeta, 
      abnormal expression of peroxiredoxins and mitochondrial structural genes were 
      prevented and mitochondrial function was normal; intact mitochondria were present 
      and neurite outgrowth was significantly increased. In primary neurons from 
      amyloid-beta precursor protein transgenic mice that were treated with MitoQ and 
      SS31, neurite outgrowth was significantly increased and cyclophilin D expression 
      was significantly decreased. These findings suggest that MitoQ and SS31 prevent 
      Abeta toxicity, which would warrant the study of MitoQ and SS31 as potential 
      drugs to treat patients with AD.
FAU - Manczak, Maria
AU  - Manczak M
AD  - Neurogenetics Laboratory, Division of Neuroscience, Oregon National Primate 
      Research Center, Oregon Health & Science University, Beaverton, OR, USA.
FAU - Mao, Peizhong
AU  - Mao P
FAU - Calkins, Marcus J
AU  - Calkins MJ
FAU - Cornea, Anda
AU  - Cornea A
FAU - Reddy, Arubala P
AU  - Reddy AP
FAU - Murphy, Michael P
AU  - Murphy MP
FAU - Szeto, Hazel H
AU  - Szeto HH
FAU - Park, Byung
AU  - Park B
FAU - Reddy, P Hemachandra
AU  - Reddy PH
LA  - eng
GR  - P51 RR000163/RR/NCRR NIH HHS/United States
GR  - RR00163/RR/NCRR NIH HHS/United States
GR  - AG026051/AG/NIA NIH HHS/United States
GR  - R01 AG028072-03/AG/NIA NIH HHS/United States
GR  - R03 AG026051/AG/NIA NIH HHS/United States
GR  - AG028072/AG/NIA NIH HHS/United States
GR  - R01 AG028072/AG/NIA NIH HHS/United States
GR  - MC_U105663142/MRC_/Medical Research Council/United Kingdom
GR  - K01 RR000163/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Antioxidants)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (RNA, Messenger)
RN  - 0 (amyloid beta-protein (25-35))
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.11.1.15 (Peroxiredoxins)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Alzheimer Disease/drug therapy/*pathology
MH  - Amyloid beta-Peptides/*toxicity
MH  - Amyloid beta-Protein Precursor
MH  - Analysis of Variance
MH  - Animals
MH  - Antioxidants/*pharmacology
MH  - Cell Line, Transformed/ultrastructure
MH  - Cell Survival/drug effects
MH  - Disease Models, Animal
MH  - Drug Interactions
MH  - Electron Transport Complex IV/metabolism
MH  - Gene Expression Regulation/*drug effects
MH  - Humans
MH  - Hydrogen Peroxide/metabolism
MH  - Lipid Peroxidation/drug effects
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mice
MH  - Mice, Transgenic
MH  - Microscopy, Electron, Transmission/methods
MH  - Mitochondria/*drug effects/ultrastructure
MH  - Mitochondrial Proteins/genetics/metabolism
MH  - Neurons/*drug effects/metabolism/pathology/ultrastructure
MH  - Peptide Fragments/*toxicity
MH  - Peroxiredoxins/genetics/metabolism
MH  - RNA, Messenger/metabolism
PMC - PMC3072711
MID - NIHMS281205
COIS- CONFLICT OF INTEREST STATEMENT Patent applications have been filed by the Cornell 
      Research Foundation Inc (CRF) for the technology (SS peptides) described in this 
      article. Hazel H Szeto is the inventor. CRF, on behalf of Cornell University, has 
      licensed the technology for further research and development to a commercial 
      enterprise in which CRF and Dr. Szeto have financial interests. Patents in the 
      MitoQ technology are being commercialized by Antipodean Pharmaceuticals in which 
      M. Murphy has a financial interest.
EDAT- 2010/05/14 06:00
MHDA- 2010/09/14 06:00
PMCR- 2011/04/08
CRDT- 2010/05/14 06:00
PHST- 2010/05/14 06:00 [entrez]
PHST- 2010/05/14 06:00 [pubmed]
PHST- 2010/09/14 06:00 [medline]
PHST- 2011/04/08 00:00 [pmc-release]
AID - 27411T412V3H0235 [pii]
AID - 10.3233/JAD-2010-100564 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2010;20 Suppl 2(Suppl 2):S609-31. doi: 10.3233/JAD-2010-100564.