Inhibition of A beta fibril formation and A beta-induced cytotoxicity by senile plaque-associated proteins.
A beta neurotoxicity is generally believed to require A beta fibril formation. The prevention of A beta fibril formation thus seems to be a promising strategy for the treatment of AD. Recent studies have shown senile plaque-associated proteins such as laminin to have an inhibitory effect on both A beta40 and A beta42 fibril formation in vitro. In the present study, we thus investigated whether or not midkine (MK) and alpha2-macroglobulin (alpha2M), both of which are also senile plaque-associated proteins like laminin, affect A beta fibril formation and A beta-induced cytotoxicity. The present study demonstrated that both MK and alpha2M inhibit both A beta fibril formation and A beta-induced cytotoxicity in PC12 cells. The confirmation of the present results based on in vivo experiments is called for in future studies to clarify whether or not senile plaque-associated proteins such as MK and alpha2M can be a model for therapeutic agents in the treatment of AD.
Monji
A
A
Department of Neuropsychiatry, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Yoshida
I
I
Tashiro
K
K
Hayashi
Y
Y
Matsuda
K
K
Tashiro
N
N
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D016207:Cytokines; D006801:Humans; D046911:Macromolecular Substances; D008854:Microscopy, Electron; D000078792:Midkine; D016716:PC12 Cells / Q000187:drug effects* / Q000648:ultrastructure; D010446:Peptide Fragments / Q000378:metabolism* / Q000633:toxicity; D058225:Plaque, Amyloid / Q000737:chemistry*; D051381:Rats; D000511:alpha-Macroglobulins / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D002352:Carrier Proteins; D016207:Cytokines; D046911:Macromolecular Substances; D010446:Peptide Fragments; D000511:alpha-Macroglobulins; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D000078792:Midkine