Anti-amyloidogenic activity of tetracyclines: studies in vitro.
Cerebral deposition of beta-amyloid is a major neuropathological feature in Alzheimer's disease. Here we show that tetracyclines, tetracycline and doxycycline, classical antibiotics, exhibit anti-amyloidogenic activity. This capacity was determined by the exposure of beta 1-42 amyloid peptide to the drugs followed by the electron microscopy examination of the amyloid fibrils spontaneously formed and quantified with thioflavine T binding assay. The drugs reduced also the resistance of beta 1-42 amyloid fibrils to trypsin digestion. Tetracyclines not only inhibited the beta-amyloid aggregates formation but also disassembled the pre-formed fibrils. The results indicate that drugs with a well-known clinical profile, including activity in the central nervous system, are potentially useful for Alzheimer's therapy.
Forloni
G
G
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. forloni@irfmn.mnegri.it
Colombo
L
L
Girola
L
L
Tagliavini
F
F
Salmona
M
M
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D052160:Benzothiazoles; D004318:Doxycycline / Q000494:pharmacology; D005456:Fluorescent Dyes; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D013752:Tetracycline / Q000494:pharmacology; D013754:Tetracyclines / Q000494:pharmacology*; D013844:Thiazoles; D014357:Trypsin / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D005456:Fluorescent Dyes; D046911:Macromolecular Substances; D010446:Peptide Fragments; D013754:Tetracyclines; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); C009462:thioflavin T; D014357:Trypsin; D013752:Tetracycline; D004318:Doxycycline