Page 230 - ebook

[C. Omics & Fusion Biology] C-3

Comparative phosphoproteomics of Neuro-2a cells

under insulin resistance reveals new molecular signatures of

Alzheimer’s disease

Yeon Suk Jo¹,², Han Seul Jo¹, Sung won Bae¹, Yang Woo Kwon¹, Dayea Kim³*, Yong Seok Oh²*, Jong

Hyuk Yoon¹*

¹Neurodegenerative Diseases Research Group, Korea Brain Research Institute, Daegu 41062, Korea, ²Department of

Brain-Cognitive Science, Daegu-Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea,
³New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea

Insulin is a well-known critical factor in brain development and the control of neurogenesis, in-cluding in the

hippocampus. The alteration of insulin signaling in the brain can induce brain aging and regulate brain plasticity
and could promote neurodegeneration in the late stage of Alzheimer’s disease (AD). The precise molecular

mechanism of the relationship between insulin resistance and AD remains unclear. The development of
phosphoproteomics has advanced our knowledge of phosphorylation-mediated signaling networks and could

elucidate the molecular mechanisms of certain conditions. Here, we applied a reliable phosphoproteomic approach
to Neuro-2a (N2a) cells to identify their molecular features under two different clinically reliable insulin-resistant

conditions: inflammation and dyslipidemia. We found different informatic characteristics between the two insulin-
resistant phosphoproteomes by comparative informatics analysis. We also found commonly changed molecular

signatures, including phosphoproteins, in the integrin and adenosine monophosphate-activated protein kinase
pathways under insulin resistance and verified these targets by subsequent biochemical experiments. Among the

commonly changed molecular signatures, the phosphorylation of acetyl-CoA carboxylase and Src was also found
to be altered in the brains of 5xFAD mice. This study provides new molecular signatures for insulin resistance in

N2a cells and possible links between the molecular features of insulin resistance and AD.