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Aβ and human amylin share a common toxicity pathway via mitochondrial dysfunction
Author(s) -
Lim YunAn,
Rhein Virginie,
Baysang Ginette,
Meier Fides,
Poljak Anne,
J. Raftery Mark,
Guilhaus Michael,
Ittner Lars M.,
Eckert Anne,
Götz Jürgen
Publication year - 2010
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200900651
Subject(s) - amylin , toxicity , mitochondrion , amyloid (mycology) , mitochondrial toxicity , amyloid beta , insulin , diabetes mellitus , biology , beta (programming language) , endocrinology , medicine , biochemistry , pharmacology , chemistry , disease , pathology , islet , computer science , programming language
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.