Proteomic Analysis Reveals Differentially Regulated Protein Acetylation in Human Amyotrophic Lateral Sclerosis Spinal CordReport as inadecuate




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



Author: Dong Liu , Chaoxu Liu , Junqiang Li , Kazem Azadzoi, Yun Yang, Zhou Fei, Kefeng Dou, Neil W. Kowall, Han-Pil Choi, Fernando Vieir

Source: http://plos.srce.hr/



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