A single protein may help treat Parkinson’s, Alzheimer’s

Scientists have found that a single protein can lead to effective treatments for devastating neurodegenerative diseases, such as Parkinson's, Huntington’s, Alzeheimer's and amyotrophic lateral sclerosis (ALS). These disorders are triggered by misbehaving proteins in the brain that misfold and accumulate in neurons, inflicting damage and eventually killing the cells. In the study, researchers from the Gladstone Institutes in California, used a different protein — Nrf2 — to restore levels of the disease-causing proteins to a normal, healthy range, thereby preventing cell death. ‘We’ve tested Nrf2 in models of Huntington’s disease, Parkinson’s disease, and ALS, and it is the most protective thing we’ve ever found. Based on the magnitude and the breadth of the effect, we really want to understand Nrf2 and its role in protein regulation better,’ said Steven Finkbeiner from Gladstone Institute. The researchers tested Nrf2 in two models of Parkinson’s disease — cells with mutations in the proteins LRRK2 and alpha-synuclein.

By activating Nrf2, the researchers turned on several ‘house-cleaning’ mechanisms in the cell to remove excess LRRK2 and alpha-synuclein. ‘Nrf2 coordinates a whole program of gene expression, but we didn’t know how important it was for regulating protein levels until now,’ added Gaia Skibinski, research scientist at Gladstone Institute. ‘Over-expressing Nrf2 in cellular models of Parkinson’s disease resulted in a huge effect. In fact, it protects cells against the disease better than anything else we’ve found,’ Skibinski explained. Using a one-of-a-kind robotic microscope, the team tagged and tracked individual neurons — both rat and human — over time to monitor their protein levels and overall health. They took thousands of images of the cells over the course of a week, measuring the development and demise of each one. While, for mutant LRRK2, Nrf2 drove the protein to gather into incidental clumps that can remain in the cell without damaging it, for alpha-synuclein, Nrf2 accelerated the breakdown and clearance of the protein, reducing its levels in the cell, the results showed. The study was published in the Proceedings of the National Academy of Sciences (PNAS). 

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