title: Proteomic analysis of brain proteins in APP/PS-1 human double mutant knock-in mice with increasing amyloid β-peptide deposition: insights into the effects of in vivo treatment with N-acetylcysteine as a potential therapeutic intervention in mild cognitive impairment and Alzheimer's disease.
abstract: Proteomics analyses were performed on the brains of wild-type (WT) controls and an Alzheimer's disease (AD) mouse model, APP/PS-1 human double mutant knock-in mice. Mice were given either drinking water or water supplemented with N-acetylcysteine (NAC) (2 mg/kg body weight) for a period of five months. The time periods of treatment correspond to ages prior to Aβ deposition (i.e. 4-9 months), resembling human mild cognitive impairment (MCI), and after Aβ deposition (i.e. 7-12 months), more closely resembling advancing stages of AD. Substantial differences exist between the proteomes of WT and APP/PS-1 mice at 9 or 12 months, indicating that Aβ deposition and oxidative stress lead to downstream changes in protein expression. Altered proteins are involved in energy-related pathways, excitotoxicity, cell cycle signaling, synaptic abnormalities, and cellular defense and structure. Overall, the proteomic results support the notion that NAC may be beneficial for increasing cellular stress responses in WT mice and for influencing the levels of energy- and mitochondria-related proteins in APP/PS-1 mice.
authors.affiliation: Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA.
authors.forename: Renã A S
authors.initials: RA
authors.lastname: Robinson
authors.forename: Gururaj
authors.initials: G
authors.lastname: Joshi
authors.forename: Quanzhen
authors.initials: Q
authors.lastname: Huang
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Sultana
authors.forename: Austin S
authors.initials: AS
authors.lastname: Baker
authors.forename: Jian
authors.initials: J
authors.lastname: Cai
authors.forename: William
authors.initials: W
authors.lastname: Pierce
authors.forename: Daret K
authors.initials: DK
authors.lastname: St Clair
authors.forename: William R
authors.initials: WR
authors.lastname: Markesbery
authors.forename: D Allan
authors.initials: DA
authors.lastname: Butterfield
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000188:drug therapy; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D055879:Gene Knock-In Techniques; D006801:Humans; D051379:Mice; D009154:Mutation; D053764:Presenilin-1 / Q000235:genetics* / Q000378:metabolism; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016166:Free Radical Scavengers; D053764:Presenilin-1; D020543:Proteome; D000111:Acetylcysteine