Anti-amyloidogenic activity of tetracyclines: studies in vitro
- FEBS Lett. 2001 Jan 5;487(3):404-7. doi: 10.1016/s0014-5793(00)02380-2.
- 1. Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. [email protected]
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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