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Updated: Jan 23, 2026
Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
In vitro degradation of β-amyloid fibrils by microbial keratinase
Debananda S Ningthoujam1, Saikat Mukherjee1, Laishram Jaya Devi1
1Department of Biochemistry, Advanced Level State Biotech Hub, Microbial Biotechnology Research Laboratory, Manipur University, Imphal, Manipur, India.
Introduction:
Amyloid fibrils are misfolded, protease-resistant forms of normal proteins. They are infectious such as prions or noninfectious such as β-amyloid (Aβ) fibrils causing Alzheimer's disease (AD). Prions and amyloids are structurally similar, possessing cross β-pleated sheet-like structures. As microbial keratinase could degrade prions, we tested keratinase activity on Aβ fibrils.
Methods:
Lysozyme treated with urea generates Aβ fibrils demonstrated by immunoblotting with anti-Aβ 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 Aβ fibrils.
Results:
Soluble Ker1 and Ker1 reconstituted on neutral/cationic liposomes degraded Aβ fibrils efficiently. Ker 2 was less potent.
Discussion:
Drugs that target AD inhibit acetylcholinesterase or formation of Aβ 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.
Insights
Microbial keratinases, particularly Ker1, show promise in degrading amyloid-beta (Aβ) fibrils, offering a novel therapeutic avenue for Alzheimer
Area of Science:
- Biochemistry
- Neuroscience
- Microbiology
Background:
- Amyloid fibrils, including infectious prions and non-infectious β-amyloid (Aβ) in Alzheimer's disease (AD), share similar cross β-pleated sheet structures.
- Microbial enzymes like keratinase have demonstrated the ability to degrade prions.
Purpose of the Study:
- To investigate the efficacy of microbial keratinases in degrading Aβ fibrils associated with Alzheimer's disease.
Main Methods:
- Aβ fibrils were generated from lysozyme using urea treatment.
- Two purified keratinases, Ker1 and Ker2, from Amycolatopsis sp. MBRL 40 were incubated with Aβ fibrils.
- Degradation was assessed using techniques including immunoblotting, HPLC, and Congo red absorption spectroscopy.
Main Results:
- Soluble Ker1 and Ker1 reconstituted on liposomes efficiently degraded Aβ fibrils.
- Ker2 exhibited lower potency in degrading Aβ fibrils compared to Ker1.
Conclusions:
- Keratinases represent novel therapeutic molecules for Alzheimer's disease drug development.
- Current AD drugs targeting acetylcholinesterase or Aβ formation have limitations, including side effects and limited cognitive benefits.
- Keratinase-based therapies offer a potential alternative with a different mechanism of action.
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