Differences between normal and alpha-synuclein overexpressing SH-SY5Y neuroblastoma cells after Abeta(1-42) and NAC treatment.
Alpha-synuclein (alphaSN) plays a major role in numerous neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. Intracellular inclusions containing aggregated alphaSN have been reported in Alzheimer's and Parkinson's affected brains. Moreover, a proteolytic fragment of alphaSN, the so-called non-amyloid component of Alzheimer's disease amyloid (NAC) was found to be an integral part of Alzheimer's dementia related plaques. Despite the extensive research on this topic, the exact toxic mechanism of alphaSN remains elusive. We have taken the advantage of an alphaSN overexpressing SH-SY5Y cell line and investigated the effects of classical apoptotic factors (e.g. H(2)O(2), amphotericin B and ruthenium red) and aggregated disease-related peptides on cell viability compared to wild type neuroblastoma cells. It was found that alphaSN overexpressing cells are more sensitive to aggregated peptides treatment than normal expressing counterparts. In contrast, cells containing elevated amount of alphaSN were less vulnerable to classical apoptotic stressors than wild type cells. In addition, alphaSN overexpression is accompanied by altered phenotype, attenuated proliferation kinetics, increased neurite arborisation and decreased cell motility. Based on these results, the alphaSN overexpressing cell lines may represent a good and effective in vitro model for Alzheimer's and Parkinson's disease.
Hunya
Akos
A
Department of Medical Chemistry, University of Szeged, Szikra utca 2, Szeged, Hungary. akos.hunya@gmail.com
Földi
István
I
Szegedi
Viktor
V
Soós
Katalin
K
Zarándi
Márta
M
Szabó
Antal
A
Zádori
Dénes
D
Penke
Botond
B
Datki
Zsolt L
ZL
D000544:Alzheimer Disease / Q000378:metabolism*; D000666:Amphotericin B / Q000494:pharmacology; D000682:Amyloid / Q000737:chemistry / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008970:Molecular Weight; D009447:Neuroblastoma / Q000378:metabolism* / Q000503:physiopathology; D010446:Peptide Fragments / Q000494:pharmacology*; D012430:Ruthenium Red / Q000494:pharmacology; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D013778:Tetrazolium Salts; D013844:Thiazoles; D051844:alpha-Synuclein; C075222:amyloid beta-protein (1-42); D012430:Ruthenium Red; D000666:Amphotericin B; D006861:Hydrogen Peroxide; C022616:thiazolyl blue