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Single Protein May Hold Secret To Treating Parkinson’s, Alzheimer’s Disease: Study

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Knowledge obtained about a novel cellular protein could help in the treatment of various neurodegenerative diseases including Parkinson's, Huntington's, Alzheimer's, and amyotrophic lateral sclerosis, reports a recent study.

Nrf2 And Neurodegenerative Diseases

The neurodegenerative diseases are usually triggered by misfolding and accumulation of proteins present in the neurons, which results in the damage and destruction of brain cells. A protein called Nrf2 could help in treating the diseases by managing the defective proteins, according to the researchers from the Gladstone Institutes.

For the purpose of the study, the investigators tested the role of Nrf2 in two different types of Parkinson's disease that include cells with mutated LRRK2 protein and mutated α-synuclein. It was observed that when Nrf2 was activated it took part in several house-keeping activities and restored the cells' functions by eliminating the mutated proteins.

Gaia Skibinski, a researcher at Gladstone, said that Nrf2 has a huge role to play in gene expression, but the importance of the protein in regulating other proteins wasn't known earlier. When Nrf2 was over-activated it helped in protecting the cells against the diseases in a way better than any other treatment found by far, noted Skibinski.

Nrf2 And Mutated α-synuclein And LRRK2

The researchers induced the pluripotent stem cells from both rats and humans to produce neural cells, which were programmed to express the protein Nrf2 and either mutant α-synuclein or LRRK2. With the help of a special robotic microscope developed by the Finkbeiner laboratory the investigators tracked the neurons for over a week, monitoring their development and functions till death.

It was observed that Nrf2 regulated the neural cell with mutated LRRK2 by gathering the abnormal proteins into a clump and storing them in one single place without letting the proteins damage the cells. Whereas, in case of mutated α-synuclein, the protein Nrf2 escalated the breakdown, destruction and clearance of α-synuclein and restored the functions of the neurons.

Nrf2 And Huntington's Disease And Parkinson's Disease

Finkbeiner said that he is very much encouraged by the study findings that could help in the treatment of the neurodegenerative diseases.

"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," said Finkbeiner, in a press release.

The researcher also noted that since it would be difficult to design a drug to target Nrf2 in the neurons, the focus will be on other players involved in the protein regulation pathway that impacts Nrf2.

The study is published in the journal Proceedings of the National Academy of Sciences.

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