The role of ferritinophagy and ferroptosis in Alzheimer's disease.

Brain Res

Dongguan Key Laboratory of Traditional Chinese Medicine and New Pharmaceutical Development, The Affiliated Dongguan Songshan Lake Central Hospital, School of Pharmacy, Guangdong Medical University, Dongguan, China. Electronic address:

Published: November 2024

Iron is a crucial mineral element within human cells, serving as a pivotal cofactor for diverse biological enzymes. Ferritin plays a crucial role in maintaining iron homeostasis within the body through its ability to sequester and release iron. Ferritinophagy is a selective autophagic process in cells that specifically facilitates the degradation of ferritin and subsequent release of free iron, thereby regulating intracellular iron homeostasis. The nuclear receptor coactivator 4 (NCOA4) serves as a pivotal regulator in the entire process of ferritinophagy, facilitating its binding to ferritin and subsequent delivering to lysosomes for degradation, thereby enabling the release of free iron. The free iron ions within the cell undergo catalysis through the Fenton reaction, resulting in a substantial generation of reactive oxygen species (ROS). This process induces lipid peroxidation, thereby stimulating a cascade leading to cellular tissue damage and subsequent initiation of ferroptosis. Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive deterioration of emotional memory and cognitive function, accompanied by mental and behavioral aberrations. The pathology of the disease is characterized by aberrant deposition of amyloid β-protein (Aβ) and hyperphosphorylated tau protein. It has been observed that evident iron metabolism disorders and accumulation of lipid peroxides occur in AD, indicating a significant impact of ferritinophagy and ferroptosis on the pathogenesis and progression of AD. This article elucidates the process and mechanism of ferritinophagy and ferroptosis, investigating their implications in AD to identify novel targets for therapeutic intervention.

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Source
http://dx.doi.org/10.1016/j.brainres.2024.149340DOI Listing

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