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Yang, Hongkuan; Yang, Mingchun; Guan, Hongpeng; Liu, Ziyi; Zhao, Shiguang; Takeuchi, Shigeko; Yanagisawa, Daijiro; Tooyama, Ikuo
Neuroscience research, 09/2013, Letnik: 77, Številka: 1-2Journal Article
•Mitochondrial ferritin (FtMt) is a novel protein localized to the mitochondria.•FtMt is expressed in restricted tissues including the brain.•FtMt lacks iron regulatory elements and its expression is increased by oxidative stress.•FtMt is increased in the cerebral cortex of AD patients and in the substantia nigra of individuals with PD and RLS.•The presence of FtMt prevents cell death induced by oxidative stress and neurotoxic proteins. Mitochondrial ferritin (FtMt) is a novel protein encoded by an intronless gene mapped to chromosome 5q23.1. Ferritin is ubiquitously expressed; however, FtMt expression is restricted to specific tissues such as the testis and the brain. The distribution pattern of FtMt suggests a functional role for this protein in the brain; however, data concerning the roles of FtMt in neurodegenerative diseases remain scarce. In the human cerebral cortex, FtMt expression was increased in Alzheimer's disease patients compared to control cases. Cultured neuroblastoma cells showed low-level expression of FtMt, which was increased by H2O2 treatment. FtMt overexpression showed a neuroprotective effect against H2O2-induced oxidative stress and Aβ-induced neurotoxicity in neuroblastoma cells. FtMt expression was also detected in dopaminergic neurons in the substantia nigra and was increased in patients with restless legs syndrome, while FtMt had a protective effect against cell death in a neuroblastoma cell line model of Parkinson's disease. FtMt is involved in other neurodegenerative diseases such as age-related macular degeneration (AMD), with an FtMt gene mutation identified in AMD patients, and Friedreich's ataxia, which is caused by a deficiency in frataxin. FtMt overexpression in frataxin-deficient cells increased cell resistance to H2O2 damage. These results implicate a neuroprotective role of FtMt in neurodegenerative diseases.
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