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(1987) first reported nigral iron elevation in PD, a finding later confirmed by X-ray microanalysis ( 2.1.2 Dysregulation of key iron-regulating proteins In ferroptosis, intracellular iron homeostasis is maintained by a network of regulatory mechanisms, including iron acquisition via the transferrin (Tf)/transferrin receptor 1 (TfR1) pathway, intracellular transport by divalent metal transporter 1 (DMT1), export by ferroportin (FPN1), storage in ferritin, and iron release through ferritinophagy mediated by nuclear receptor coactivator 4 (NCOA4) ( Iron acquisition typically begins with extracellular ferric iron (Fe 3+ ) binding to Tf, forming a Tf-Fe 3+ complex that is internalized through TfR1-mediated endocytosis ( Inside the endosome, Fe 3+ is reduced to Fe 2+ by ferrireductases like six-transmembrane epithelial antigen of prostate 3 (STEAP3), and the resulting Fe 2+ is then transported into the cytoplasm primarily by DMT1 ( + ) dopaminergic neurons compared with 53% and 58% loss in wild-type (+/+) and heterozygous (+/mk) mice, respectively

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