Gene mutation that traffics iron in the brain linked to Parkinson's Disease
Mutations in the LRRK2 gene, which cause some forms of Parkinson’s disease, were found to misdirect iron in activated microglia in a new study published in the journal PLOS Biology.
The study was led by Mark Cookson, PhD, of the National Institute of Aging. In mouse astrocytes with a LRRK2 pathogenic mutation, researchers observed a protein known as Rab8a. Rab8a regulates the transportation process of iron into the cell through the transferrin receptor. Once the receptor has released its transferrin and iron, Rab8a then helps the receptor be reabsorbed by the membrane.
The study’s results suggested that the LRRK2 mutation redirected the location of RAb8a from the endocytic recycling compartment to damaged lysosomes. This caused the transferrin receptor and the iron it carried to pile up at the damaged lysosomes as well. When tested in activated microglia derived from human cells carrying the same pathogenic LRRK2 mutation, again, Rab8a was mislocated and the transferrin receptor followed. Researchers also injected mice carrying the mutation with a proinflammatory trigger. Results showed a significant increase in iron expelled in microglia in the striatum, an area of the brain that’s significantly affected by Parkinson’s disease.
The study suggests that mutations in the LRRK2 gene, as they relate to Parkinson’s disease, interfere with the regulation of iron in the brain. These findings may explain iron build up in parts of the brain affected by the disease and help with future treatments.