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Abeta‐polyacrolein is neurotoxic in an amyloid‐independent manner
Author(s) -
Theisen Christopher Shane,
Seidler Norbert W
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.752.5
Subject(s) - neurotoxicity , downregulation and upregulation , chemistry , transient receptor potential channel , amyloid (mycology) , receptor , microbiology and biotechnology , gene , cancer research , toxicity , biochemistry , biology , inorganic chemistry , organic chemistry
A previous study indicated that amyloid beta peptide (ABP) exhibits surfactant properties, suggesting that the toxicity of ABP in Alzheimer disease (AD) is attributed to the peptide's effect on the organization of water molecules. We previously proposed that ABP‐polyacrolein, which is derived from ABP‐induced polymerization of acrolein, may contribute to the neurotoxicity in AD. In this study, we examined the effect of ABP‐polyacrolein on gene expression in differentiated SH‐SY5Y cells using a PCR array composed of probes for 84 genes that are involved in neurotoxicity. We compared the results against the effects of ABP alone. We observed that ABP alone decreased the expression of eight different genes (criterion: greater than 2‐fold change). However, the downregulation of three of these genes (epiregulin, tryptophan hydroxylase‐1, and transient receptor potential cation channel‐M4) were appreciably attenuated by ABP‐polyacrolein presumably due to ABP‐polyacrolein's abrogation of ABP's surfactant‐like injury to the cell. Furthermore, we observed a unique downregulation of three genes with ABP‐polyacrolein (hephaestin, notch 4, and transient receptor potential cation channel‐M1). This suggests a novel mechanism of neurotoxicity not seen with ABP alone and likely due to the extensive polymeric arrangement of ABP‐polyacrolein, which is quite dissimilar from the typical amyloid structure.