Unknown

Dataset Information

0

Proteomic identification of specifically carbonylated brain proteins in APP(NLh)/APP(NLh) × PS-1(P264L)/PS-1(P264L) human double mutant knock-in mice model of Alzheimer disease as a function of age.


ABSTRACT: Alzheimer disease (AD) is the most common type of dementia and is characterized pathologically by the presence of neurofibrillary tangles (NFTs), senile plaques (SPs), and loss of synapses. The main component of SP is amyloid-beta peptide (A?), a 39 to 43 amino acid peptide, generated by the proteolytic cleavage of amyloid precursor protein (APP) by the action of beta- and gamma-secretases. The presenilins (PS) are components of the ?-secretase, which contains the protease active center. Mutations in PS enhance the production of the A?42 peptide. To date, more than 160 mutations in PS1 have been identified. Many PS mutations increase the production of the ?-secretase-mediated C-terminal (CT) 99 amino acid-long fragment (CT99), which is subsequently cleaved by ?-secretase to yield A? peptides. A? has been proposed to induce oxidative stress and neurotoxicity. Previous studies from our laboratory and others showed an age-dependent increase in oxidative stress markers, loss of lipid asymmetry, and A? production and amyloid deposition in the brain of APP/PS1 mice. In the present study, we used APP (NLh)/APP(NLh) × PS-1(P246L)/PS-1(P246L) human double mutant knock-in APP/PS-1 mice to identify specific targets of brain protein carbonylation in an age-dependent manner. We found a number of proteins that are oxidatively modified in APP/PS1 mice compared to age-matched controls. The relevance of the identified proteins to the progression and pathogenesis of AD is discussed.

SUBMITTER: Sultana R 

PROVIDER: S-EPMC3199338 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

Proteomic identification of specifically carbonylated brain proteins in APP(NLh)/APP(NLh) × PS-1(P264L)/PS-1(P264L) human double mutant knock-in mice model of Alzheimer disease as a function of age.

Sultana Rukhsana R   Robinson Renã A S RA   Di Domenico Fabio F   Abdul Hafiz Mohmmad HM   St Clair Daret K DK   Markesbery William R WR   Cai Jian J   Pierce William M WM   Butterfield D Allan DA  

Journal of proteomics 20110625 11


Alzheimer disease (AD) is the most common type of dementia and is characterized pathologically by the presence of neurofibrillary tangles (NFTs), senile plaques (SPs), and loss of synapses. The main component of SP is amyloid-beta peptide (Aβ), a 39 to 43 amino acid peptide, generated by the proteolytic cleavage of amyloid precursor protein (APP) by the action of beta- and gamma-secretases. The presenilins (PS) are components of the γ-secretase, which contains the protease active center. Mutatio  ...[more]

Similar Datasets

| S-EPMC4848925 | biostudies-literature
| S-EPMC3517055 | biostudies-literature
| S-EPMC4122804 | biostudies-literature
| S-EPMC6826143 | biostudies-literature
| S-EPMC10777534 | biostudies-literature
| S-EPMC4100935 | biostudies-literature
| S-EPMC6002862 | biostudies-literature
| S-EPMC8244172 | biostudies-literature
| S-EPMC7719723 | biostudies-literature
| S-EPMC2880535 | biostudies-literature