Promotion of formation of amyloid fibrils by aluminium adenosine triphosphate (AlATP).
The formation of amyloid fibrils is considered to be an important step in the aetiology of Alzheimer's disease and other amyloidoses. Fibril formation in vitro has been shown to depend on many different factors including modifications to the amino acid profile of fibrillogenic peptides and interactions with both large and small molecules of physiological significance. How these factors might contribute to amyloid fibril formation in vivo is not clear as very little is known about the promotion of fibril formation in undersaturated solutions of amyloidogenic peptides. We have used thioflavin T fluorescence and reverse phase high performance liquid chromatography to show that ATP, and in particular AlATP, promoted the formation of thioflavin T-reactive fibrils of beta amyloid and, an unrelated amyloidogenic peptide, amylin. Evidence is presented that induction of fibril formation followed the complexation of AIATP by one or more monomers of the respective peptide. However, the complex formed could not be identified directly and it is suggested that AlATP might be acting as a chaperone in the assembly of amyloid fibrils. The effect of AlATP was not mimicked by either AlADP or AlAMP. However, it was blocked by suramin, a P2 ATP receptor antagonist, and this has prompted us to speculate that the precursor proteins to beta amyloid and amylin may be substrates or receptors for ATP in vivo.
Exley
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Birchall Centre for Inorganic Chemistry and Materials Science, School of Chemistry and Physics, Keele University, Staffordshire, UK. cha38@keele.ac.uk
Korchazhkina
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D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000209:etiology; D000682:Amyloid / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D016229:Amyloid beta-Peptides / Q000378:metabolism; D052160:Benzothiazoles; D005456:Fluorescent Dyes; D006801:Humans; D058228:Islet Amyloid Polypeptide; D009942:Organometallic Compounds / Q000494:pharmacology*; D013498:Suramin / Q000494:pharmacology; D013844:Thiazoles
D000682:Amyloid; D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D005456:Fluorescent Dyes; D058228:Islet Amyloid Polypeptide; D009942:Organometallic Compounds; D013844:Thiazoles; C439352:aluminum adenosine triphosphate; C009462:thioflavin T; D013498:Suramin; D000241:Adenosine