Glial cells improve Parkinson's disease by modulating neuronal function and regulating neuronal ferroptosis

Abstract

The main characteristics of Parkinson's disease (PD) are the loss of dopaminergic (DA) neurons and abnormal aggregation of cytosolic proteins. However, the exact pathogenesis of PD remains unclear, with ferroptosis emerging as one of the key factors driven by iron accumulation and lipid peroxidation. Glial cells, including microglia, astrocytes, and oligodendrocytes, serve as supportive cells in the central nervous system (CNS), but their abnormal activation can lead to DA neuron death and ferroptosis. This paper explores the interactions between glial cells and DA neurons, reviews the changes in glial cells during the pathological process of PD, and reports on how glial cells regulate ferroptosis in PD through iron homeostasis and lipid peroxidation. This opens up a new pathway for basic research and therapeutic strategies in Parkinson's disease.

Keywords: Parkinson’s disease; astrocyte; dopaminergic neuron; ferroptosis; glia-neuron interaction; glial cell; microglia; oligodendrocyte.

FIGURE 1

Schematic showing the modes of ferroptosis caused by Glia-neuron interactions in the PD brain. The brain of PD is associated with ferroptosis. Activated reactive astrocytes, microglia, and oligodendrocytes can undergo inflammatory reactions, causing oxidative stress, exacerbating neurotoxicity, and affecting the health of dopaminergic neurons. Meanwhile, abnormally activated glial cells further interact with neurons by affecting transferrin to exacerbate iron deposition and lipid peroxidation, ultimately leading to ferroptosis.