Acetylcholinesterase, a senile plaque component, affects the fibrillogenesis of amyloid-beta-peptides.
Acetylcholinesterase (AChE) colocalizes with amyloid-beta peptide (A beta) deposits present in the brain of Alzheimer's patients. Recent studies showed that A beta 1-40 can adopt two different conformational states in solution (an amyloidogenic conformer, A beta ac, and a non-amyloidogenic conformer, A beta nac) which have distinct abilities to form amyloid fibrils. We report here that AChE binds A beta nac and accelerates amyloid formation by the same peptide. No such effect was observed with A beta ac, the amyloidogenic conformer, suggesting that AChE acts as a 'pathological chaperone' inducing a conformational transition from A beta nac into A beta ac in vitro.
Alvarez
A
A
Departamento de Biología Celular y Molecular, Pontificia Universidad Católica de Chile, Santiago.
Bronfman
F
F
Pérez
C A
CA
Vicente
M
M
Garrido
J
J
Inestrosa
N C
NC
D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D001923:Brain Chemistry; D006801:Humans; D016874:Neurofibrillary Tangles / Q000201:enzymology / Q000473:pathology*; D011487:Protein Conformation
D016229:Amyloid beta-Peptides; D000110:Acetylcholinesterase