Protein Found Effective Against Parkinson's Disease

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Highlights

• Scientists working on neurodegenerative diseases have identified a key protein, Nrf2, that prevents the accumulation of proteins that damage the neurons in the brain.
• Both LRRK2 or α-synuclein proteins that are implicated in Parkinson's and Alzheimer's, after the addition of Nrk2, were either clumped together or removed from the cell, preventing damage to the cell.
• Nrk2 has the potential to be used as the first treatment measure for neurodegenerative disorders.

A key cellular protein identified by latest research studies could be the cure for many neurodegenerative disorders like Huntington's, Parkinson's, Alzheimer's and Amyotrophic Lateral Sclerosis These disorders are caused by protein folding and accumulation in the neurons, resulting in the damage to the cells and finally destruction.

Dr. Steven Finkbeiner and colleagues from The Gladstone Institute used another protein called the Nrf2 which brings the rogue, disease causing proteins in the brain to normal levels, thus avoiding damage and killing of essential neurons.

‘Nrf2 is a key protein can remove toxic proteins and could be effective against neurodegenerative diseases’

Testing in Parkinson's Disease Cells

The protein was tested on two versions of Parkinson's disease cells, one type of cells with mutations in the protein LRRK2 and the other type of cells with mutations in the protein α-synuclein. The researchers found that when the protein Nrf2 was activated, it lead to a �housekeeping' of the cell that resulted in removal of the excess of LRRK2 and α-synuclein.

Dr. Gaia Skibinski who is the first author of the study and a staff research scientist at Gladstone Institute says that Nrf2 has always been known to regulate gene expression but its function in lowering levels of other proteins was not known till now. The overexpression of the protein Nrf2 was found to be very beneficial in Parkinson's disease and protected the cells from damage much better than any method till date.

The study was published in the Journal Proceedings of the National Academy of Sciences detailing the effect of the protein Nrf2 in lowering the levels of other proteins. In the study, both rat neurons and human neurons were induced from pluripotent stem cells.

The neuron cells were programmed to express

• Nrf2 protein
• Either LRRK2 or α-synuclein protein

The researchers used a microscope that was developed by the Finkbeiner laboratory to study the cells that were tagged to monitor the level of protein. The overall health of the cells was also monitored. The researchers took many pictures of the cells, from development till they died.

The protein Nrf2 worked in differing ways to lower levels of the two proteins

• For cells with mutant LRRK2, the LRRK2 proteins were clumped together and they remained in the cell without damaging it.
• For cells with mutant α-synuclein, the α-synuclein breakdown was accelerated and the protein cleared from the cells.

Dr.Finkbeiner who is the senior author of the study said that he was very excited about this research study and that they had used the protein Nrf2 on cells with Parkinson's, Huntington's and ALS and found effective protection which was not identified with any other method of protection. The senior researcher further added "Based on the magnitude and the breadth of the effect, we really want to understand Nrf2 and its role in protein regulation better".

The identification of the protein Nrf2 is significant in the research studies on neurodegenerative diseases. It holds promise in the treatment of these diseases, however, the protein cannot be used as the target for drug therapy. This is because the protein is involved in multiple metabolic processes. The scientists are looking at downstream elements which could act as possible targets.

Nrf2:

The Nrf2 is the nuclear factor erythroid 2 protein that is involved in antioxidant signaling. This protein controls basal as well as induced protein in the array of antioxidant response element- developmental genes to regulate the response to anti-oxidants.

These proteins are not involved in blood cell differentiation but they are found to regulate certain drug metabolizing enzymes. Their primary role is in the resistance to oxidative stress. The protein is known to be anti-inflammatory and results in age dependent autoimmunity in mice. There are many benefits that have been identified, the most important being in chronic obstructive pulmonary disease (COPD). Heavy cigarette smokers are at an increased risk of getting COPD, but the protein Nrf2 is found to be protective against damage to the lungs.

The protective effect of this protein has been well established; the current study that unearthed benefits in neurodegenerative disorders will have a profound effect on the treatment and care of these diseases. Neurodegenerative disorders are debilitating conditions that affect the quality of life of the individual, but there is no known cure for these conditions yet. The use of this protein in the treatment of these diseases could help treat the conditions. Further studies could detail whether the use of this protein as a preventive medicine restricts accumulation of toxic proteins in the brain that leads to neuronal damage.

References

1. The Nrf2-Antioxidant Response Element Signaling Pathway and Its Activation by Oxidative Stress - (https:www.ncbi.nlm.nih.gov/pmc/articles/PMC4680839/)
2. Role of Nrf2 in Oxidative Stress and Toxicity - (https:www.ncbi.nlm.nih.gov/pmc/articles/PMC2679427/)

Source: Medindia

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