PMID- 20186753
OWN - NLM
STAT- MEDLINE
DCOM- 20100805
LR  - 20220317
IS  - 1615-9861 (Electronic)
IS  - 1615-9853 (Linking)
VI  - 10
IP  - 8
DP  - 2010 Apr
TI  - Abeta and human amylin share a common toxicity pathway via mitochondrial 
      dysfunction.
PG  - 1621-33
LID - 10.1002/pmic.200900651 [doi]
AB  - Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are leading causes 
      of morbidity and mortality in the elderly. Both diseases are characterized by 
      amyloid deposition in target tissues: aggregation of amylin in T2DM is associated 
      with loss of insulin-secreting beta-cells, while amyloid beta (A beta) 
      aggregation in AD brain is associated with neuronal loss. Here, we used 
      quantitative iTRAQ proteomics as a discovery tool to show that both A beta and 
      human amylin (HA) deregulate identical proteins, a quarter of which are 
      mitochondrial, supporting the notion that mitochondrial dysfunction is a common 
      target in these two amyloidoses. A functional validation revealed that 
      mitochondrial complex IV activity was significantly reduced after treatment with 
      either HA or A beta, as was mitochondrial respiration. In comparison, complex I 
      activity was reduced only after treatment with HA. A beta and HA, but not the 
      non-amyloidogenic rat amylin, induced significant increases in the generation of 
      ROS. Co-incubation of HA and A beta did not produce an augmented effect in ROS 
      production, again suggesting common toxicity mechanisms. In conclusion, our data 
      suggest that A beta and HA both exert toxicity, at least in part, via 
      mitochondrial dysfunction, thus restoring their function may be beneficial for 
      both AD and T2DM.
FAU - Lim, Yun-An
AU  - Lim YA
AD  - Alzheimer's & Parkinson's Disease Laboratory, Brain & Mind Research Institute, 
      University of Sydney, Camperdown, Australia.
FAU - Rhein, Virginie
AU  - Rhein V
FAU - Baysang, Ginette
AU  - Baysang G
FAU - Meier, Fides
AU  - Meier F
FAU - Poljak, Anne
AU  - Poljak A
FAU - Raftery, Mark J
AU  - Raftery MJ
FAU - Guilhaus, Michael
AU  - Guilhaus M
FAU - Ittner, Lars M
AU  - Ittner LM
FAU - Eckert, Anne
AU  - Eckert A
FAU - Gotz, Jurgen
AU  - Gotz J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Proteomics
JT  - Proteomics
JID - 101092707
RN  - 0 (Amyloid)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Islet Amyloid Polypeptide)
RN  - 0 (Reactive Oxygen Species)
SB  - IM
MH  - Amyloid/*metabolism
MH  - Amyloid beta-Peptides/*metabolism
MH  - Cell Line, Tumor
MH  - Humans
MH  - Islet Amyloid Polypeptide
MH  - Mitochondria/*metabolism
MH  - Oxygen Consumption
MH  - Reactive Oxygen Species/metabolism
EDAT- 2010/02/27 06:00
MHDA- 2010/08/06 06:00
CRDT- 2010/02/27 06:00
PHST- 2010/02/27 06:00 [entrez]
PHST- 2010/02/27 06:00 [pubmed]
PHST- 2010/08/06 06:00 [medline]
AID - 10.1002/pmic.200900651 [doi]
PST - ppublish
SO  - Proteomics. 2010 Apr;10(8):1621-33. doi: 10.1002/pmic.200900651.