Researchers have used a non-invasive method of observing how the process leading to Parkinson’s disease takes place at the nanoscale, and identified the point in the process at which proteins in the brain become toxic, eventually leading to the death of brain cells.
The results suggest that the same protein can either cause, or protect against, the toxic effects that lead to the death of brain cells, depending on the specific structural form it takes, and that toxic effects take hold when there is an imbalance of the level of protein in its natural form in a cell. The work could help unravel how and why people develop Parkinson’s, and aid in the search for potential treatments. The study is published in the journal Proceedings of the National Academy of Sciences.
Using super-resolution microscopy, researchers were able to observe the behaviour of different types of alpha-synuclein, a protein closely associated with Parkinson’s disease, in order to find how it affects neurons, and at what point it becomes toxic.
Parkinson’s disease is one of a number of neurodegenerative diseases caused when naturally occurring proteins fold into the wrong shape and stick together with other proteins, eventually forming thin filament-like structures called amyloid fibrils. These amyloid deposits of aggregated alpha-synuclein, also known as Lewy bodies, are the hallmark of Parkinson’s disease.
Parkinson’s disease is the second-most common neurodegenerative disease worldwide (after Alzheimer’s disease). More than seven million people worldwide have the disease. Symptoms include muscle tremors, stiffness and difficulty walking. Dementia is common in later stages of the disease.
The researchers used different forms of alpha-synuclein and observed their behaviour in neurons from rats. They were then able to correlate what they saw with the amount of toxicity that was present.
They found that when they added alpha-synuclein fibrils to the neurons, they interacted with alpha-synuclein protein that was already in the cell, and no toxic effects were present.
The researchers then observed that by adding the soluble form of alpha-synuclein together with amyloid fibrils, the toxic effect of the former could be overcome. It appeared that the amyloid fibrils acted like magnets for the soluble protein and mopped up the soluble protein pool, shielding against the associated toxic effects.
The research shows how important it is to fully understand the processes at work behind neurodegenerative diseases, so that the right step in the process can be targeted.
Source: Adapted from materials provided by the University of Cambridge
„Nanoscopic insights into seeding mechanisms and toxicity of α-synuclein species in neurons“