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Potential treatment for Parkinson’s Disease

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Ayanna Tucker reports from Johns Hopkins University:

Researchers from the Johns Hopkins University School of Medicine have helped develop a nanobody capable of getting through the tough exterior of brain cells and untangling misshapen proteins that lead to Parkinson’s disease, Lewy body dementia, and other neurocognitive disorders.

The research, published last month in Nature Communications, was led by Xiaobo Mao, an associate professor of neurology at the School of Medicine, and included scientists at the University of Michigan, Ann Arbor. Their aim was to find a new type of treatment that could specifically target the misshapen proteins, called alpha-synuclein, which tend to clump together and gum up the inner workings of brain cells. Emerging evidence has shown that the alpha-synuclein clumps can spread from the gut or nose to the brain, driving the disease progression.

Nanobodies—miniature versions of antibodies, which are proteins in the blood that help the immune system find and attack foreign pathogens—are natural compounds in the blood of animals such as llamas and sharks and are being studied to treat autoimmune diseases and cancer in humans. In theory, antibodies have the potential to zero in on clumping alpha-synuclein proteins, but have a hard time getting through the outer covering of brain cells. To squeeze through these tough brain cell coatings, the researchers decided to use nanobodies instead.

The researchers had to shore up the nanobodies to help them keep stable within a brain cell. To do this, they genetically engineered them to rid them of chemical bonds that typically degrade inside a cell. Tests showed that without the bonds, the nanobody remained stable and was still able to bind to misshapen alpha-synuclein.

The team made seven similar types of nanobodies, known as PFFNBs, that could bind to alpha-synuclein clumps. Of the nanobodies they created, one—PFFNB2—did the best job of glomming onto alpha-synuclein clumps and not single molecules, or monomer of alpha-synuclein, which are not harmful and may have important functions in brain cells.

Additional tests in mice showed that . . .

Continue reading.

Written by Leisureguy

3 August 2022 at 9:34 am

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