Find out how proteins mutate in Parkinson's disease
Researchers have figured out how the proteins that cause Parkinson's disease spread in the brain.A new study has revealed how mutated proteins that are a hallmark of Parkinson's disease spread and aggregate in the brain. This will help develop new methods to stop the progression of this and other neurodegenerative diseases caused by protein aggregation.
The link between neurodegenerative disorders, aggregation and the spread of proteins such as alpha-synuclein (AF) is well understood. But it remains unclear whether aggregation or proliferation is primary. A new study by scientists from Toiko University of Medicine and Dentistry has provided answers.
To see how AF monomers and fibrils move around the brain, the researchers injected a small amount of mutated alpha-synuclein with green fluorescent protein into the brains of mice. Since any cell can help spread AF, they used viral particles to allow its synthesis in cells at the injection site.
Two weeks after injection, the researchers noticed fluorescence in distant areas of the brain away from the injection site, indicating the spread of monomeric mutated alpha synuclein. They found the fluorescent protein in the glyphatic system, a unique arrangement of channels that carries proteins and metabolites out of the central nervous system, and noticed that it was taken up by neurons. A year later, the monomers stuck together to form fibrils.
"The alpha-synuclein fibrils formed after the monomers multiplied," explains Hitoshi Okazawa, an author of the study. - Specifically, we observed alpha-synuclein monomer in the glymphatic system and distant regions as early as two weeks after injection, and we detected alpha-synuclein fibrils 12 months after injection!"
The researchers noted that the amount of alpha-synuclein aggregation and the time it took for it to form varied and was not proportional to the distance from the injection site.
More than 20 years ago, scientists discovered that the protein alpha-synuclein plays a crucial role in the development of Parkinson's disease. Toxic mutated AF is thought to stick together to form Levi's corpuscles, leading to progressive neuronal death. Alpha-synuclein is also involved in the second most common form of dementia after Alzheimer's disease - dementia with Levi's corpuscles.
The study is published in the journal Cell Reports.