Scientists are better equipped to study diseases such as Alzheimer’s and Parkinson’s
- Post by: CIPPS
- 19 September 2023
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Amyloid fibrils are formed when normally healthy and soluble proteins misfold and stick together to form species that cannot be broken down. It is well known that these structures cause toxicity that can lead to a range of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. These diseases are extremely difficult to treat and there are still very few drugs which target amyloid structures. One of the reasons it is so hard to develop such drugs is that amyloids are very difficult to visualise and study.
Amyloid fibrils are generally around 10 nm in diameter and can grow to micrometres in length with diverse structures. This means they cannot be viewed under traditional microscopes, as objects smaller than 200 nm will blur together due to the way light is bent through the lenses of the microscope.
Instead, specialised microscopy techniques that detect fluorescence can be used to visualise much smaller structures. These techniques require a special fluorescent probe, which is a molecule that will fluoresce when it meets a particular trigger or structure.
Last year, CIPPS AI Amandeep Kaur, along with CIPPS CI Liz New and Dr Liam Adair, published a new fluorescent probe that can be used to accurately detect amyloid fibrils. The probe, called AmyBlink-1, contains one section which fluoresces green when attached to specific grooves in amyloid structures and another section which always fluoresces red. The ratio green to red fluorescence therefore reports on the amount of amyloid fibril: when the probe is near fibrils, the ratio is much higher. The ratio can therefore be used to produce a super-resolution image of amyloid fibrils. Sophisticated mathematical analyses can also be undertaken to give more structural information about the fibrils.
This innovative new probe is already being used by groups in Cambridge and the Australian Institute for Bioengineering and Nanotechnology in Queensland to research Alzheimer’s and Parkinson’s diseases.