Figure 4.

Iron and inflammation are intertwined in a bidirectional relationship during neurodegeneration. The neurodegenerative process starts with the loss of immune homeostatic mechanisms, partially due to decreased norepinephrine (NE) neurotransmission after the degeneration of the locus coeruleus (LC) (1). It continues with neuronal death in intrinsically sensitive areas, such as the substantia nigra (SN) (2a) and the entorhinal cortex (2b), fueled by a positive feedback loop between neuroinflammation, oxidative stress, and iron accumulation (the wheel at the center). As the disease progresses, neurodegeneration continues to other brain regions, such as the hippocampus and the cortex (4). Hepcidin can suppress the main pathologies in experimental Alzheimer’s disease (AD) and Parkinson’s disease (PD) through the inhibition of iron entry at the blood–brain barrier (BBB) (3). Created with BioRender.com.