Think of the brain like a city where trash must be regularly disposed of to keep the streets clean and functional. In Parkinson's disease, something similar happens to proteins in the brain. Normally, unwanted or damaged proteins are disposed of through the “cellular garbage disposal”. But in Parkinson's disease, these proteins build up and cause problems.

A special protein called NEMO plays an important role here. It works like a garbage collector who recognizes special markings on the proteins to be disposed of. These marks are made up of chains of small molecules called ubiquitin. Depending on the structure of these ubiquitin chains, NEMO knows how to break down the proteins.

Parkinson's patients accumulate special protein aggregates known as Lewy bodies, which are composed primarily of a protein called α-synuclein. These aggregates can be toxic to nerve cells and cause these cells to die.

NEMO helps by docking onto these aggregates and supporting their breakdown. This occurs through cooperation with other parts of the cellular waste disposal system, particularly a process called autophagy. During autophagy, unwanted materials are packaged into bubbles and then broken down in the lysosomes, the cell's “waste incinerators.”

Researchers have found that a mutation in the NEMO gene causes a severe form of Parkinson's disease in some people. This mutation prevents NEMO from binding properly to the ubiquitin chains and thus supporting the breakdown of the harmful protein aggregates. The result is an accumulation of these aggregates in the brain, which worsens the course of the disease.

These findings are important because they open up new possibilities for the treatment of Parkinson's. By understanding how NEMO works, scientists may be able to develop new therapies that target this protein, helping to reduce the buildup of harmful protein aggregates in the brain prevent or to reduce.

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