TY - JOUR
T1 - The inflammation-sensitive protein alpha 1-anti-chymotrypsin neutralizes fibrillar aggregation and cytotoxicity of the beta-amyloid peptide more effectively than alpha 1-antitrypsin
AU - Giunta, S.
AU - Galeazzi, R.
AU - Marcellini, M.
AU - Corder, E. H.
AU - Galeazzi, L.
PY - 2007/8
Y1 - 2007/8
N2 - Objectives: A neuroinflammatory process, triggered by amyloid-beta (Aβ)-peptide, is thought to play a central role in the neurodegenerative process leading to Alzheimer's disease (AD). Aβ25-35 retains the functionality of Aβ42 and was employed to investigate the effects of inflammation-sensitive proteins (ISPs) α1-antichymotrypsin (A1ACT) and α1-antitrypsin (A1AT) on fibrillar aggregation and cytotoxicity. Design and methods: Inhibitory concentrations of the ISPs were determined in an established human red blood cell lysis model of Aβ-cytotoxicity. For studies of Aβ-fibrillar aggregation CSF levels of A1ACT (0.041 μM)/A1AT (0.11 μM) were incubated with Congo Red dye 25 μM + Aβ25-35 10 μM noting the formation of visible aggregates and spectrophotometric changes over 24 h. Results: A1ACT at CSF reported levels inhibited fibrillar aggregation and cytotoxicity while A1AT at CSF reported levels failed to cause a similar inhibition. Conclusions: A1ACT neutralizes fibrillar aggregation and cytotoxicity of Aβ-peptide more effectively than A1AT. Both proteins are known to be co-deposited with Aβ within senile plaques of AD brains.
AB - Objectives: A neuroinflammatory process, triggered by amyloid-beta (Aβ)-peptide, is thought to play a central role in the neurodegenerative process leading to Alzheimer's disease (AD). Aβ25-35 retains the functionality of Aβ42 and was employed to investigate the effects of inflammation-sensitive proteins (ISPs) α1-antichymotrypsin (A1ACT) and α1-antitrypsin (A1AT) on fibrillar aggregation and cytotoxicity. Design and methods: Inhibitory concentrations of the ISPs were determined in an established human red blood cell lysis model of Aβ-cytotoxicity. For studies of Aβ-fibrillar aggregation CSF levels of A1ACT (0.041 μM)/A1AT (0.11 μM) were incubated with Congo Red dye 25 μM + Aβ25-35 10 μM noting the formation of visible aggregates and spectrophotometric changes over 24 h. Results: A1ACT at CSF reported levels inhibited fibrillar aggregation and cytotoxicity while A1AT at CSF reported levels failed to cause a similar inhibition. Conclusions: A1ACT neutralizes fibrillar aggregation and cytotoxicity of Aβ-peptide more effectively than A1AT. Both proteins are known to be co-deposited with Aβ within senile plaques of AD brains.
KW - Alpha1-anti-trypsin
KW - Alpha1-antichymotrypsin
KW - Alzheimer pathogenesis
KW - Amyloid-β
KW - Erythrocyte-cytotoxicity
KW - Fibrillar aggregation
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U2 - 10.1016/j.clinbiochem.2007.03.026
DO - 10.1016/j.clinbiochem.2007.03.026
M3 - Article
C2 - 17512513
AN - SCOPUS:34447536419
VL - 40
SP - 887
EP - 892
JO - Clinical Biochemistry
JF - Clinical Biochemistry
SN - 0009-9120
IS - 12
ER -