Proteomic Analysis Reveals Differentially Regulated Protein Acetylation in Human Amyotrophic Lateral Sclerosis Spinal Cord

摘要: Amyotrophic lateral sclerosis (ALS) is a progressive fatal neurodegenerative disease that primarily affects motor neurons in the brain and spinal cord. Histone deacetylase (HDAC) inhibitors have neuroprotective effects potentially useful for treatment of diseases including ALS; however, molecular mechanisms underlying their potential efficacy not well understood. Here we report protein acetylation urea-soluble proteins differently regulated post-mortem ALS Two-dimensional electrophoresis (2-DE) analysis reveals several clusters with similar weight but different charge status. Liquid chromatography tandem mass spectrometry (LC-MS/MS) identifies glial fibrillary acidic (GFAP) as dominant component clusters. Further indicates six heavily acetylated lysine residues at positions 89, 153, 189, 218, 259 331 GFAP. Immunoprecipitation followed by Western blotting confirms larger form GFAP fragments are upregulated studies demonstrate additional to regulated, suggesting and/or deacetylation play an important role pathogenesis ALS.