S-nitrosation of proteins relevant to Alzheimer’s disease during early stages of neurodegeneration

ABSTRACT: Protein S-nitrosation (SNO-protein) is a post-translational modification in which a cysteine (Cys) residue is modified by nitric oxide (SNO-Cys). SNO-proteins impact many biological systems, but their identification has been technically challenging. We developed a chemical proteomic strategy - SNOTRAP (SNO trapping by triaryl phosphine) -that allows improved identification of SNO-proteins by mass spectrometry. We found that S-nitrosation is elevated during early stages of neurodegeneration, preceding cognitive decline. We identified changes in the SNOproteome during early neurodegeneration that are potentially relevant for synapse function, metabolism, and Alzheimer’s disease pathology. SNO-proteome analysis further reveals a potential linear motif for SNO-Cys sites that are altered during neurodegeneration. Our strategy can be applied to multiple cellular and disease contexts and can reveal signaling networks that aid drug development.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

DISEASE(S): Alzheimer's Disease

SUBMITTER: John Wishnok  

LAB HEAD: Steven R. Tannenbaum

PROVIDER: PXD003802 | Pride | 2016-03-31

REPOSITORIES: Pride