Axonopathy Underlying Neurodegeneration In The Central Nervous System Under the Impact of Iron Dyshomeostasis

Authors

• K Arvind
• TA Rouault

Abstract

Iron-regulatory protein 2 (IREB2, aka IRP2) plays a significant role in regulating metabolic processes, including energy production in the central nervous system (CNS). The brain has unique mechanisms for regulating iron homeostasis, with regions like the cortex being particularly sensitive to changes in iron levels. Cortical neurons in the CNS are involved in synaptic plasticity, a critical process for learning, memory, cognition, and decision-making. Our recent findings in human IREB2-/- patients highlight severe neurodegenerative diseases.

Through this study, we aim to investigate the molecular mechanisms underlying axonopathy in the CNS under the impact of iron dyshomeostasis. We observed that in adulthood, IRP2-/- mice develop a movement disorder characterized by ataxia, bradykinesia, and tremor. IRP2-null mice show a significant increase in the expression of the iron sequestration protein ferritin and pronounced colocalization of ferric iron accumulation with axonopathy. Overall, the absence of IRP2 impacts neuronal health in the CNS, predisposing neurons to degeneration. Our study is a concerted effort to delve into the molecular events in axonopathy and answer the question of how iron dysregulation causes neurodegenerative disease in IREB2-/- patients.

Scientific Focus Area: Neuroscience

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