MicroRNA miR-29 controls a compensatory response to limit neuronal iron accumulation during adult life and aging

• DOI: 10.1101/046516
• Publication Date: 2016-04-01T05:45:18Z
• Authors: Roberto Ripa; Luca Dolfi; Marco Terrigno; Luca Pandolfini; Valeria Arcucci; Marco Groth; Eva Tozzini Terzi...; Mario Baumgart; Alessandro Cellerino
• Keywords: Homeostasis; Transferrin receptor

Abstract Iron is an essential metal cofactor for enzymes involved in many cellular functions such as energy generation and cell proliferation. However, excessive iron concentration leads to increased oxidative stress toxicity. As such, homeostasis strictly controlled by two RNA binding proteins known Regulatory Proteins (IRPs) that regulate at post-transcriptional level the expression of management genes. Despite this fine regulation, impairment occurs during aging: progressively accumulates several organs turn, it exacerbates vulnerability tissue decay. Moreover, accumulation within CNS observed neurodegenerative diseases. We investigated age-dependent changes using short lived fish Nothobranchius furzeri. Here, we show i) both content microRNA family miR-29 increase adult life aging N. furzeri brain; ii) up-regulates brain murine neurons, while turn targets 3′-UTR IREB2 mRNA, reducing intake; iii) Transgenic with knock-down significant adult-onset up-regulation IRP2 its target TFR1 neurons display enhanced iron; iv) triggers a global gene response partially overlaps induced aging. Our studies indicate modulates intracellular up-regulated adaptive limit prevent early-onset processes.