tailieunhanh - Báo cáo khoa học: Neuronal growth-inhibitory factor (metallothionein-3): evaluation of the biological function of growth-inhibitory factor in the injured and neurodegenerative brain

Neuronal growth-inhibitory factor, later renamed metallothionein-3, is one of four members of the mammalian metallothionein family. Metallothione-ins are a family of ubiquitous, low-molecular-weight, cysteine-rich proteins. Although neuronal growth-inhibitory factor shares metal-binding and reac-tive oxygen species scavenging properties with the other metallothioneins, it displays several distinct biological properties. , | ỊFEBS Journal MINIREVIEW Neuronal growth-inhibitory factor metallothionein-3 evaluation of the biological function of growth-inhibitory factor in the injured and neurodegenerative brain Claire Howells Adrian K. West and Roger S. Chung Menzies Research Institute University of Tasmania Hobart Australia Keywords brain injury metals neuronalgrowth-inhibitory factor GIF neurodegenerative disease oxidative stress Correspondence R. S. Chung PhD Private Bag 58 University of Tasmania Hobart Tasmania 7001 Australia Fax 61 3 62262703 Tel 61 3 62262657 E-mail rschung@ Neuronal growth-inhibitory factor later renamed metallothionein-3 is one of four members of the mammalian metallothionein family. Metallothione-ins are a family of ubiquitous low-molecular-weight cysteine-rich proteins. Although neuronal growth-inhibitory factor shares metal-binding and reactive oxygen species scavenging properties with the other metallothioneins it displays several distinct biological properties. In this review we examine the recent developments regarding the function of neuronal growth-inhibitory factor within the brain particularly in response to brain injury or during neurodegenerative disease progression. Received 27 November 2009 revised 13 March 2010 accepted 19 May 2010 doi Introduction Metallothioneins MTs are a family of unusual cysteine-rich 30 6-7 kDa proteins synthesized predominantly by astrocytes within the brain. The MT3 isoform was first isolated and identified as a neuronal growth-inhibitory factor GIF in 1991 a brain-specific protein whose synthesis was notably deficient in the Alzheimer s disease AD brain. It was found to possess a strong ability to impair neurite outgrowth and neuronal survival of cultured neurons leading to its designation as GIF. It was later discovered that GIF shares approximately 70 amino-acid sequence similarity with the MT family of proteins leading to its renaming as MT3. Most striking is the conservation .