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Scientists engineer nanobody to untangle brain proteins linked with Parkinson’s

Scientists engineer nanobody to untangle brain proteins linked with Parkinson’s

Mini versions of antibodies can break through tough brain cells and untangle alpha-synuclein proteins linked with several neurological disorders
man holding brain, future of health care
Representational image | Shutterstock

Researchers from The Johns Hopkins University School of Medicine and the University of Ann Arbor have engineered a nanobody that can untangle misshapen proteins in brain cells that have been known to lead to neurodegenerative diseases like Parkinson’s, Alzheimer’s, and Lewy Body Dementia. 

These genetically engineered nanobodies, mini versions of antibodies found naturally in the blood of llamas and sharks, target clumps proteins that regulates the release of neurotransmitters in the brain, which have long been associated with neurodegenerative diseases. 

While our bodies naturally produce antibodies that can untangle these proteins, they have a hard time to get through the exterior of brain cells. The nanobody that was designed by the team was able to break through these barriers in brain cells of mice and untangle the alpha-synuclein protein.

While promising, a lot more work will be needed before this can be approved for trials in humans.

Designated PFFNB2, the nanobody was found to target only clumped-up masses of proteins and not its monomers. 

“The success of PFFNB2 in binding harmful alpha-synuclein clumps in increasingly complex environments indicates that the nanobody could be key to helping scientists study these diseases and eventually develop new treatments,” said Xiaobo Mao, associate professor of neurology at The Johns Hopkins University School of Medicine. 

ALSO READ: Swiss success in imaging proteins linked to Parkinson’s raises drugs hope 

Explaining how the nanobodies work, the researchers said that they engineered it to remove chemical bonds that would typically degrade inside a cell. The tests they conducted showed that these bonds remained stable inside the brain cells, while still being able to bind with and untangle the misshapen alpha-synuclein proteins. 

However, the team’s successive testing on mice revealed that the nanobody could not prevent the formation of new masses of the proteins, but it can destabilise existing ones. 

“It (the nanobody) prevented alpha-synuclein clumps from spreading to the mouse brain’s cortex, the region responsible for cognition, movement, personality, and other high-order processes,” said Ramhari Kumbhar, a lead author who worked on the study from the team at The Johns Hopkins University School of Medicine. 

The researchers said that the development could lead to novel methods of treating neurological disorders such as Parkinson’s, Alzheimer’s and Lewy Body Dementia, which currently don’t have a cure. 

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