Protective effects of EUK4010 on beta-amyloid(1-42) induced degeneration of neuronal cells.
EUK4010 has been identified to exhibit an inhibitory effect on beta-amyloid (Abeta)(1-42)-induced loss of neuronal cell viability. Further studies demonstrated that EUK4010 attenuated the Abeta(1-42)-induced degeneration in both cultured rat hippocampal neurons and human neuroblastoma cells, as demonstrated by typical morphological changes, cell viability and the chip-based flow cytometric assay. Gene expression analysis using DNA microarray showed that the senescence marker calcium-binding protein, regucalcin (Rgn), GABA-A receptor pi subunit (Gabrp), the huntingtin binding protein, optineurin (Optn) and a semaphorin family plexin A3 similar protein (Plex-similar) changed their expression levels significantly in cultured neurons after Abeta(1-42) treatment. In this report, we have undertaken a chemical genetic approach to study the molecular basis of Abeta(1-42) effects on the neuronal degeneration. Our results demonstrate that EUK4010 completely blocked the Abeta(1-42)-induced up-regulation of GABA-A receptor pi subunit and the semaphorin family plexin A3 similar protein, and partially attenuated the down-regulation of senescence marker calcium-binding protein, regucalcin. These observations suggest that EUK4010 may prevent or reduce the Abeta toxicity by regulating the expression of genes involved in the Abeta induced neuronal degeneration. These genes may represent a promising target for the therapeutic drug development for Alzheimer's disease (AD) and other neurological disorders. Furthermore, EUK4010 and its analogues could potentially be developed as neuronal protective agents for the treatment of these diseases.
Sun
Liwen
L
Biophysics lab of Brain Function, College of Life Sciences, Zhejiang University, Hangzhou 310027, China.
Wang
Li
L
Sun
Yong
Y
Tang
Syao-Wei
SW
Hu
Yinghe
Y
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D001688:Biological Products / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008516:Medicine, Chinese Traditional; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D001688:Biological Products; D015415:Biomarkers; C517651:EUK4010; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)