The Effects of Endogenous Non-Peptide Molecule Isatinand Hydrogen Peroxide on Proteomic Profilingof Rat Brain Amyloid-β Binding Proteins:Relevance to Alzheimer’s Disease?

International Journal of Molecular Sciences

Olga A. Buneeva¹  Oksana V. Gnedenko¹  Alexis S. Ivanov¹  Alexei E. Medvedev¹  Arthur T. Kopylov¹  Victor G. Zgoda¹  Sergey A. Kozin²  Alexander A. Makarov²  Marina V. Medvedeva³ 

[1] Department of Proteomic Research and Mass Spectrometry, Institute of Biomedical Chemistry,10 Pogodinskaya Street, Moscow 119121, Russia;Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia;School of Biology, Lomonosov Moscow State University, Moscow 119191, Russia;

关键词: amyloid-β;    amyloid-β binding proteins;    proteomic profiling;    rat brain;    isatin;    oxidative stress;   

DOI  :  10.3390/ijms16010476

来源: DOAJ

【 摘 要 】

The amyloid-β peptide is considered as a key player in the development and progression of Alzheimer’s disease (AD). Although good evidence exists that amyloid-β accumulates inside cells, intracellular brain amyloid-binding proteins remain poorly characterized. Proteomic profiling of rat brain homogenates, performed in this study, resulted in identification of 89 individual intracellular amyloid-binding proteins,and approximately 25% of them were proteins that we had previously identifiedas specifically binding to isatin, an endogenous neuroprotector molecule. A significant proportion of the amyloid-binding proteins (more than 30%) are differentially expressedor altered/oxidatively modified in AD patients. Incubation of brain homogenates with70 µM hydrogen peroxide significantly influenced the profile of amyloid-β binding proteins and 0.1 mM isatin decreased the number of identified amyloid-β binding proteins both in control and hydrogen peroxide treated brain homogenates. The effects of hydrogen peroxide and isatin have been confirmed in optical biosensor experiments with purified glyceraldehyde-3-phosphate dehydrogenase, one of the known crucial amyloid-β binding proteins (also identified in this study). Data obtained suggest that isatin protects crucial intracellular protein targets against amyloid binding, and possibly favors intracellular degradation of this protein via preventing formation of amyloid-β oligomers described in the literature for some isatin derivatives.

【 授权许可】

Unknown