Iron imbalance is a key factor in neurodegenerative diseases, with both iron overload and deficiency contributing to neuronal death through mechanisms such as oxidative stress, membrane damage, and mitochondrial dysfunction. Iron is essential for brain functions, but its dysregulation can lead to neurodegeneration. The brain's iron distribution is heterogeneous, with higher concentrations in the basal ganglia and lower in other regions. Iron enters the brain through the blood-brain barrier (BBB) via transferrin (Tf) and non-transferrin-bound iron (NTBI), and is regulated by proteins like TfR1, DMT1, and ferritin. Iron homeostasis is tightly controlled by systemic pathways, but brain iron regulation is less understood. Aging and neuroinflammation contribute to iron accumulation in specific brain regions, exacerbating neurodegeneration. Iron dysregulation is implicated in various neurodegenerative diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), and multiple sclerosis (MS). Iron overload and deficiency can trigger pathways leading to neuronal death, with ferroptosis being a key mechanism involving lipid peroxidation and oxidative stress. Iron-related disorders, such as Neurodegeneration with Brain Iron Accumulation (NBIA), highlight the role of iron in neurodegeneration. Therapeutic approaches targeting iron imbalance, such as iron chelators, have shown some success in certain diseases, but more research is needed to fully understand the complex relationship between iron and neurodegeneration. Understanding iron's role in neurodegeneration is crucial for developing effective treatments.Iron imbalance is a key factor in neurodegenerative diseases, with both iron overload and deficiency contributing to neuronal death through mechanisms such as oxidative stress, membrane damage, and mitochondrial dysfunction. Iron is essential for brain functions, but its dysregulation can lead to neurodegeneration. The brain's iron distribution is heterogeneous, with higher concentrations in the basal ganglia and lower in other regions. Iron enters the brain through the blood-brain barrier (BBB) via transferrin (Tf) and non-transferrin-bound iron (NTBI), and is regulated by proteins like TfR1, DMT1, and ferritin. Iron homeostasis is tightly controlled by systemic pathways, but brain iron regulation is less understood. Aging and neuroinflammation contribute to iron accumulation in specific brain regions, exacerbating neurodegeneration. Iron dysregulation is implicated in various neurodegenerative diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), and multiple sclerosis (MS). Iron overload and deficiency can trigger pathways leading to neuronal death, with ferroptosis being a key mechanism involving lipid peroxidation and oxidative stress. Iron-related disorders, such as Neurodegeneration with Brain Iron Accumulation (NBIA), highlight the role of iron in neurodegeneration. Therapeutic approaches targeting iron imbalance, such as iron chelators, have shown some success in certain diseases, but more research is needed to fully understand the complex relationship between iron and neurodegeneration. Understanding iron's role in neurodegeneration is crucial for developing effective treatments.