Presymptomatic alterations in energy metabolism and oxidative stress in the APP23 mouse model of Alzheimer disease

Journal of Proteome Research
Daniela HartlMichael Rohe

Abstract

Glucose hypometabolism is the earliest symptom observed in the brains of Alzheimer disease (AD) patients. In a former study, we analyzed the cortical proteome of the APP23 mouse model of AD at presymptomatic age (1 month) using a 2-D electrophoresis-based approach. Interestingly, long before amyloidosis can be observed in APP23 mice, proteins associated with energy metabolism were predominantly altered in transgenic as compared to wild-type mice indicating presymptomatic changes in energy metabolism. In the study presented here, we analyzed whether the observed changes were associated with oxidative stress and confirmed our previous findings in primary cortical neurons, which exhibited altered ADP/ATP levels if transgenic APP was expressed. Reactive oxygen species produced during energy metabolism have important roles in cell signaling and homeostasis as they modify proteins. We observed an overall up-regulation of protein oxidation status as shown by increased protein carbonylation in the cortex of presymptomatic APP23 mice. Interestingly, many carbonylated proteins, such as Vilip1 and Syntaxin were associated to synaptic plasticity. This demonstrates an important link between energy metabolism and synaptic function, which is ...Continue Reading

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Citations

Apr 3, 2014·Journal of Neuroscience Research·Muthusamy ThangavelRanga N Parthasarathy
Jul 23, 2015·Molecular Neurobiology·Ewa NiedzielskaMałgorzata Filip
Dec 12, 2012·Journal of Proteome Research·Stephan KlattDaniela Hartl
Apr 11, 2018·Oxidative Medicine and Cellular Longevity·Joanna WojsiatUrszula Wojda
Jan 15, 2021·Biomedicines·Simon M BellHeather Mortiboys

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