The location and cause of protein malfunction in Parkinson's disease

Parkinson's is a progressive neurodegenerative disease that causes tremors, slowed movement, stiffness, and can progress to severe cognitive problems

Parkinson's disease is caused by the loss of neurons in specific parts of the brain

In a paper published today (August 30) in the journal Nature Neuroscience, the team of scientists developed a new sensitive method to study what happens to alpha-synuclein in the early stages of disease

Using neurons derived from cells donated by people with the genetic form of Parkinson's and healthy individuals, the team was able to visualize where, why and how the protein began to misfold and accumulate within nerve cells

The interdisciplinary team of neuroscientists, chemists and structural biologists discovered that alpha-synuclein contacts the membrane, or lining, of structures within nerve cells

A large number of proteins then accumulate on the surface of the mitochondria, damaging the surface of the mitochondria, causing pores to form in the membrane and interfering with the mitochondria's ability to create energy

While there are multiple subtypes of Parkinson's, the protein is known to misfold and clump together in all subtypes

Sonia Gandhi, lead author and senior group leader at Crick University and Professor of Neurology at UCL's Queen Square Institute of Neurology, said: "Great progress has been made in understanding protein misfolding, but the main challenge is research The first stage of this process in human cells

Andrey Abramov, professor at the Queen's Square Institute of Neurology at UCL, added: "We have known for some time that mitochondria are abnormal in Parkinson's disease, but the reasons for this have not been clear

Lead author Minee Choi, a senior postdoctoral researcher at the University of the Crick, said: "Our study used neurons derived from cells from Parkinson's patients, which means that the neurons we studied have the same genetic makeup and characteristics

Matthew Horrocks, co-lead author and Senior Lecturer in Biophysical Chemistry at the University of Edinburgh, added: "We have been able to use a range of state-of-the-art biophysical techniques to study how proteins misfold and cause damage in extremely complex biological samples, which is very impressive.

The innovative new method developed by the researchers can also be used to study protein misfolding in other neurodegenerative diseases and cell types, including glial cells involved in neurodegenerative diseases

The team will continue their work to study how protein misfolding within cells affects cell function and health

Minee L.