Aβ and human amylin share a common toxicity pathway via mitochondrial dysfunction

Lim, Yun-An, Rhein, Virginie, Baysang, Ginette, Meier, Fides, Poljak, Anne, Raftery, Mark J., Guilhaus, Michael, Ittner, Lars M., Eckert, Anne and Gotz, Jürgen (2010) Aβ and human amylin share a common toxicity pathway via mitochondrial dysfunction. Proteomics, 10 8: 1621-1633. doi:10.1002/pmic.200900651


Author Lim, Yun-An
Rhein, Virginie
Baysang, Ginette
Meier, Fides
Poljak, Anne
Raftery, Mark J.
Guilhaus, Michael
Ittner, Lars M.
Eckert, Anne
Gotz, Jürgen
Title Aβ and human amylin share a common toxicity pathway via mitochondrial dysfunction
Journal name Proteomics   Check publisher's open access policy
ISSN 1615-9853
1615-9861
Publication date 2010-01-01
Sub-type Article (original research)
DOI 10.1002/pmic.200900651
Volume 10
Issue 8
Start page 1621
End page 1633
Total pages 13
Place of publication Weinheim, Germany
Publisher Wiley - V C H Verlag
Language eng
Abstract 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 β-cells, while amyloid β (Aβ) aggregation in AD brain is associated with neuronal loss. Here, we used quantitative iTRAQ proteomics as a discovery tool to show that both Aβ 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 Aβ, as was mitochondrial respiration. In comparison, complex I activity was reduced only after treatment with HA. Aβ and HA, but not the non-amyloidogenic rat amylin, induced significant increases in the generation of ROS. Co-incubation of HA and Aβ did not produce an augmented effect in ROS production, again suggesting common toxicity mechanisms. In conclusion, our data suggest that Aβ and HA both exert toxicity, at least in part, via mitochondrial dysfunction, thus restoring their function may be beneficial for both AD and T2DM.
Keyword Alzheimer's disease
Amyloidosis
Mitochondrial complex proteins
Respiration
Type 2 diabetes mellitus
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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