Anti-amyloidogenic activity of tetracyclines: studies in vitro |
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Authors: | Forloni G Colombo L Girola L Tagliavini F Salmona M |
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Institution: | Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. forloni@irfmn.mnegri.it |
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Abstract: | 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. |
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