Researchers at the Perelman School of Medicine at the University of Pennsylvania report that a protein called glycoprotein nonmetastatic melanoma B (GPNMB) may help drive the cell-to-cell spread of Parkinson’s-related alpha-synuclein pathology in lab models. In cultured-neuron experiments, antibodies designed to block GPNMB reduced the propagation of the toxic process, according to a study the team says was published in Neuron.
Researchers at the Perelman School of Medicine at the University of Pennsylvania say they have identified GPNMB—short for glycoprotein nonmetastatic melanoma B—as an immune-related protein involved in the progression of Parkinson’s disease.
According to Penn Medicine and a research summary distributed by ScienceDaily, the team found that microglia—the brain’s resident immune cells—produce increased amounts of GPNMB when they are near injured or dying neurons. Enzymes can then cleave part of the protein from the cell surface, allowing a soluble form of GPNMB to move between cells.
The researchers propose that this contributes to a self-reinforcing cycle in which alpha-synuclein clumps damage neurons, prompting microglia to release more GPNMB, which in turn enhances the spread of alpha-synuclein pathology. In preclinical laboratory experiments using cultured neurons, the team reported that antibodies designed to block GPNMB prevented alpha-synuclein pathology from spreading from one cell to another.
The Penn Medicine release also describes an analysis of 1,675 human brains from the Penn Brain Bank, reporting that genetic variants associated with higher GPNMB production were linked with more extensive alpha-synuclein pathology, and that elevated GPNMB was not associated with markers tied to other neurodegenerative diseases such as Alzheimer’s.
The researchers emphasized that the findings are preliminary and would require additional work before any potential therapy could be tested in people.
