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

Lim, Yun-An and Rhein, Virginie and Baysang, Ginette and Meier, Fides and Poljak, Anne and Raftery, Mark J. and Guilhaus, Michael and Ittner, Lars M. and Eckert, Anne and Götz, Jürgen. (2010) Abeta and human amylin share a common toxicity pathway via mitochondrial dysfunction. Proteomics, Vol. 10, H. 8. pp. 1621-1633.

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Official URL: http://edoc.unibas.ch/dok/A6005840

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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.
Faculties and Departments:03 Faculty of Medicine > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Erwachsenenpsychiatrie (Lang)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Erwachsenenpsychiatrie (Lang)
UniBasel Contributors:Eckert, Anne
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Wiley-VCH Verlag
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:07 Dec 2012 13:03
Deposited On:07 Dec 2012 13:02

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