A research team from the Institut de Neurociències at the Universitat Autònoma de Barcelona (INc-UAB) has found that immune cells in the brain, called microglia, become reactive and overexpress certain receptors in patients with Parkinson's disease. This change may lead to the removal of dopaminergic neurons, even when these neurons are still functional.
The study analyzed tissue from Parkinson's disease patients as well as animal and cellular models. It focused on a specific type of receptor known as Fc gamma, which is found on the membrane of microglial cells. Under normal circumstances, these receptors help microglia identify and remove damaged cells or harmful substances from the brain.
Researchers observed that in Parkinson's disease, there is an increased density of Fc gamma receptors on reactive microglia. The team suggests that this overexpression may cause microglia to mistakenly target healthy neurons for elimination.
"When Fc gamma receptors are activated upon detecting dopaminergic neurons, even those that are still functioning, they cause the microglial cell to change shape through the activation of a cytoskeletal protein called Cdc42. This allows the microglia to surround the target neuron and literally 'eat' it, in a process known as phagocytosis," according to the research team.
The findings indicate that immunotherapy aimed at regulating microglial phagocytosis—by targeting either Fc gamma receptors or their downstream signaling protein Cdc42—could slow down disease progression and help preserve remaining dopaminergic neurons.
