Originally Posted by RLSmi

Madelyn, thanks very much for this reference.

It is beginning to look like the main activity of the normal LRRK2 protein is in the periphery of the body rather than in the brain, and is present at highest levels in circulating immune cells, and has been found to regulate the production of inflammatory cytokines by those cells.

However, the PD-related mutant LRRK2 molecules appear to have lost this regulatory function. As a result, these cytokines are chronically over produced and released into the blood. Because the cytokines, especially the one called TNF alpha can easily pass through the blood brain barrier, they apparently activate microglial cells which surround the dopaminergic neurons of the substantia nigra.

These researchers think that the resulting chronic glial cell inflammatory process damages and eventually wipes out those particular neurons.

There are lots of additional details of this new hypothesis in the paper.

Robert