Mechanism Of Entangled Proteins helps Design Parkinson's Disease Treatment

Discovery of a key way Parkinson's disease spreads in the brain may help in devising new therapies and improving the quality of life for people with Parkinson's disease. By showing how entangled proteins in brain cells enable the neurodegenerative disease to spread, it is speculated that this will lead to the development of drugs that halt its progression, as per a study at the University Of Guelph, published in the journal Cell Reports. Parkinson's disease (PD) is a progressive neurodegenerative disorder that primarily affects movement due to loss of nerve cells – neurons that produce a chemical messenger (neurotransmitter) in the brain called dopamine (black substance).

PD is characterized by the formation of inclusion proteins called Lewy bodies, triggered by the misfolding of a protein called alpha-synuclein that accumulates in a part of the brain called the substantia nigra.

Parkinson's disease is the world's fastest-growing neurodegenerative disease and Canada has some of the world's highest rates, according to Parkinson Canada. Its exact cause is unknown with no complete treatment of the disease.

Molecular Target for Parkinson’s Protein

The study team utilized stem cells to model neurons with and without Parkinson's disease and look at the effects of synuclein mutations.

It was found that in Parkinson's neurons, misfolded synuclein binds to another protein called LC3B. Normally, LC3B targets misfolded proteins to be degraded. In Parkinson's disease, the study showed, LC3 gets trapped in the protein aggregates and is inactivated.

Without degradation, the cells eject the aggregates, which then spread to nearby neurons, propagating the disease throughout the brain. Thus it was shown that activating LC3B restores degradation, enabling cells to clear the misfolded proteins and prevent disease spread.

"Normally misfolded proteins are degraded. We found a pathway by which synuclein is being secreted and released from neurons instead of being degraded. We hope to turn the degradation pathway back on and stop the spread of disease," says Dr. Scott Ryan, a professor in the Department of Molecular and Cellular Biology who led the study.

The team affirmed that their finding could help in devising therapies. Although the diseased parts of the brain cannot be reversed, further progression can be stopped and hereby provide a target for potential drug development.

However other biochemical pathways might also be involved in the spread of the disease through the brain. "Most current therapies centre around increasing the release of dopamine, but that works for a brief period and has a lot of side effects. Reduced quality of life can be a huge burden on patients, their families and the health-care system," says Ryan.

Many patients are diagnosed with PD in their 40s or 50s, indicating that they live with the progressive disease for decades. Hence the present research may help improve the quality of life for Parkinson's patients.

Source-Medindia