Deciphering the detailed structure of Parkinson's disease-causing proteins, researchers open up new ways to develop new drugs

Parkinson's disease (PD) is a common neurodegenerative disease that affects at least one in every 100 people over the age of 60

Scientists studying the pathogenesis of Parkinson's disease have discovered that mutations in a protease called LRRK2 are one of the key causes of familial and occasional Parkinson's disease

A few days ago, the top academic journal "Cell" published a research paper online.

Protease LRRK2 participates in a variety of cellular physiological processes.

In view of the importance of LRRK2, some previous studies have already understood part of the domain of LRRK2 protein

"There are about 600 kinases in the human body, and all kinases look very similar.

The high-resolution structure of full-length LRRK2 allows researchers to identify some "disease hotspots" in the molecule, where multiple mutations known to cause disease occur

One of the most common mutant forms of LRRK2 is called G2019S, which is known to cause Parkinson's disease

▲Full-length LRRK2 structure in inactivated state (picture source: reference [1])

More importantly, the researchers not only determined the structure of a single LRRK2 molecule (ie "monomer"), but also determined the structure of two connected LRRK2 molecules (ie, "dimers"), which provides for further study of the functions of LRRK2

"Under real physiological conditions, LRRK2 is only active in its dimer form," Dr.

Using this structure, the researchers also proposed a new treatment for Parkinson's disease

Note: The original text has been deleted

Reference

[1] Alexander Myasnikov et al.

[2] Structure of enzyme that causes Parkinson's promises pathways to new drugs.