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Scientists discover molecular mechanisms of Parkinson’s disease

June 13 (UPI) — Using detailed brain cell analysis, researchers have found how a protein is possibly linked to Parkinson’s disease.

Researchers in Britain and New York discovered how clumps of alpha-synuclein protein are toxic to neurons, and the role that toxicity plays in the development of Parkinson’s. Their findings were published Monday in the journal Nature Communications.

Each year, about 50,000 people are diagnosed with Parkinson’s disease, a neurodegenerative disorder in which brain cells progressively die.

Previously, scientists knew that Parkinson’s disease is associated with a build-up of alpha-synuclein protein inside brain cells, but they didn’t know how they caused the neurons to die.

“Our findings give us huge insight into why protein clumping is so damaging in Parkinson’s, and highlight the need to develop therapies against the toxic form of alpha-synuclein, not the healthy non-clumped form,” co-senior author Dr. Sonia Gandhi, a group Leader at Francis Crick Institute and University College London, said in a press release.

In the study, scientists compared healthy and clumped forms of the protein.

The researchers found that clumps of the protein move toward and then damage key proteins on the surface of mitochondria — which create energy in cells — causing them to be less efficient. From the damage, a channel on the surface of mitochondria then opens. With swelling and bursting, the mitochondria then leak chemicals that tell the cell to die.

The researchers replicated the findings by turning inducible pluripotent stem cells derived from patient’s skin cells into human brain cells that have a mutation in the alpha-synuclein gene.

This process allowed researchers to study the earliest stages of neurodegeneration, which brain scans and post-mortem analysis don’t detect.

“This study was a complex collaboration at the interface of chemistry, biophysics and biology, bringing scientists from different disciplines together to investigate a longstanding problem in Parkinson’s research,” said Dr. Andrey Abramov, co-senior author and a member of the Department of Molecular Neuroscience at UCL.

Several efforts to limit alpha-synuclein clumping in Parkinson’s patients are in the development stage right now. A vaccine-like candidate, from Austrian biotech AFFiRiS, binds to alpha-synuclein and subsequently clears it from the brain, and two other anti-body candidates have similar tactics, the Michael J. Fox Foundation for Parkinson’s research reported.

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