2010/02/22 by Yun‐An Lim, Virginie Rhein, Ginette Baysang +7 · 1 citation
Medicine · Biochemistry, Genetics and Molecular Biology · #Alzheimer's disease research and treatments #Mitochondrial Function and Pathology #Dementia and Cognitive Impairment Research
paper · doi:10.1002/pmic.200900651
openalex publication_date 2010/02/22 · openalex created_date 2016/06/24 · openalex updated_date 2026/07/29
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.