Researchers from the Gladstone Institute have identified a key cellular protein that could potentially be exploited to work as a possible treatment for neurodegenerative diseases, such as Huntington's, Parkinson's, Alzheimer's and amyotrophic lateral sclerosis.

Their findings, published in the journal Proceedings of the National Academy of Sciences, showed that the protein Nrf2 could prevent the development of neurodegenerative disease by restoring the levels of disease-causing proteins to a normal, healthy range.

"Nrf2 coordinates a whole program of gene expression, but we didn't know how important it was for regulating protein levels until now," said Gaia Skibinski, PhD, a staff research scientist at Gladstone Institute and first author of the study, in a press release. "Overexpressing 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."

Usually, neurodegenerative diseases occur when proteins in the brain misbehave. The proteins misfold and accumulate in neurons, inflicting damage and eventually damaging the brain.

For the study, the researchers tested Nrf2 in two models of Parkinson's disease. The first model has cells with mutations in the protein LRRK2, while the second model has the mutations in their α-synuclein. Using both rat neurons and human neurons created from induced pluripotent stem cells; the researchers program these neurons to express Nrf2 and either mutant LRRK2 or α-synuclein.

The researchers found that the Nrf2 protein have different mechanisms acting out to remove either the LRRK2 or α-synuclein mutations. For mutant LRRK2, Nrf2 drove the protein to gather into incidental clumps that can remain in the cell without damaging it. For α-synuclein, Nrf2 accelerated the breakdown and clearance of the protein, reducing its levels in the cell.

When the researchers tested the Nrf2 in models of Alzheimer's disease, Huntington's disease and ALS, the protein showed that it very effective in its role in protein regulation. However, the researchers noted that more research is needed to determine how the Nrf2 protein could be activated using certain drugs.