The inflammation-sensitive protein alpha 1-anti-chymotrypsin neutralizes fibrillar aggregation and cytotoxicity of the beta-amyloid peptide more effectively than alpha 1-antitrypsin.
OBJECTIVE
A neuroinflammatory process, triggered by amyloid-beta (Abeta)-peptide, is thought to play a central role in the neurodegenerative process leading to Alzheimer's disease (AD). Abeta(25-35) retains the functionality of Abeta(42) and was employed to investigate the effects of inflammation-sensitive proteins (ISPs) alpha1-antichymotrypsin (A1ACT) and alpha1-antitrypsin (A1AT) on fibrillar aggregation and cytotoxicity.


METHODS
Inhibitory concentrations of the ISPs were determined in an established human red blood cell lysis model of Abeta-cytotoxicity. For studies of Abeta-fibrillar aggregation CSF levels of A1ACT (0.041 microM)/A1AT (0.11 microM) were incubated with Congo Red dye 25 microM+Abeta(25-35) 10 microM 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 Abeta-peptide more effectively than A1AT. Both proteins are known to be co-deposited with Abeta within senile plaques of AD brains.
Giunta
S
S
Laboratorio Analisi Chimico-Cliniche, Microbiologiche e Diagnostica Molecolare, Ospedale Geriatrico INRCA (IRCCS), via della Montagnola 81, 60100, Ancona, Italy. s.giunta@inrca.it
Galeazzi
R
R
Marcellini
M
M
Corder
E H
EH
Galeazzi
L
L
D000328:Adult; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects; D003224:Congo Red; D004912:Erythrocytes / Q000187:drug effects; D006801:Humans; D007249:Inflammation; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity; D020836:Protein Structure, Quaternary; D013053:Spectrophotometry; D000514:alpha 1-Antichymotrypsin / Q000494:pharmacology*; D000515:alpha 1-Antitrypsin / Q000494:pharmacology*
D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D000514:alpha 1-Antichymotrypsin; D000515:alpha 1-Antitrypsin; C074636:amyloid beta-protein (25-35); D003224:Congo Red