ABSTRACT
INTRODUCTION: Amyloid fibrils are misfolded, protease-resistant forms of normal proteins. They are infectious such as prions or noninfectious such as ß-amyloid (Aß) fibrils causing Alzheimer's disease (AD). Prions and amyloids are structurally similar, possessing cross ß-pleated sheet-like structures. As microbial keratinase could degrade prions, we tested keratinase activity on Aß fibrils. METHODS: Lysozyme treated with urea generates Aß fibrils demonstrated by immunoblotting with anti-Aß antibody, high-performance liquid chromatography, and Congo red absorption spectroscopy. Two keratinases, Ker1 and Ker2, were purified from an actinomycete Amycolatopsis sp. MBRL 40 and incubated with Aß fibrils. RESULTS: Soluble Ker1 and Ker1 reconstituted on neutral/cationic liposomes degraded Aß fibrils efficiently. Ker 2 was less potent. DISCUSSION: Drugs that target AD inhibit acetylcholinesterase or formation of Aß fibrils and downstream effects. These drugs have side effects and do not benefit globally in cognition. Keratinases are novel molecules for drug development against AD.
