Deep Phosphoproteomic measurements pinpointing drug induced protective mechanisms in neuro-2a cells

ABSTRACT: Alzheimer's disease (AD) is a progressive and irreversible neurological disorder which impairs the living quality of old people and even life spans. New compounds have shown potential inneuroprotective effects in AD, such as GFKP-19, which is a 2-pyrrolidone derivative, which has been proved to enhance the memory of dysmnesia mouse. The molecular mechanisms remains to be established for these drug candidates. Large-scale phosphoproteomic approach has been evolved rapidly in the last several years, which should provide useful toolkit to understand cellular signaling underlying drug effects. To establish and test such a method framework, we accurately analyzed the deep quantitative phosphoproteome of the neuro-2a cells treated with or without GFKP-19 using triple SILAC labeling. A total of 14,761 class I phosphosites were quantified between control, damaged, and protected conditions using the high resolution mass spectrometry, with a high inter-mass spectrometer reproducibility for even subtle regulation events. Our data suggests that GFKP-19 can reverse Aβ25-35 caused phosphorylation change in neuro-2a cells, and might perform the neuronal protective effect by decreasing tau protein phosphorylation through down-regulating the phosphorylation level of MAPK14 at T180.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Chengli Yu  

LAB HEAD: Department of Analytical Chemistry and CAS Key Laboratory of Receptor Research

PROVIDER: PXD005312 | Pride | 2017-01-16

REPOSITORIES: Pride