Zinc Metabolism in the Brain: Relevance to Human Neurodegenerative Disorders ☆

摘要: Zinc is an important trace element in biology. An pool of zinc the brain one present synaptic vesicles a subgroup glutamatergic neurons. In this form it can be released by electrical stimulation and may serve to modulate responses at receptors for number different neurotransmitters. These include both excitatory inhibitory receptors, particularly NMDA GABA(A) receptors. This only readily stained histochemically (the chelatable pool), but constitutes about 8% total content brain. The remainder more or less tightly bound proteins where acts either as component catalytic site enzymes structural capacity. metabolism regulated transport proteins, some which have been recently characterized gene cloning techniques. intracellular concentration mediated efflux from cell transporter ZrT1 complexing with apothionein metallothlonein. Metallothionein source incorporation into including DNA transcription factors. However, metallothionein disulfides, increasing concentrations are formed under oxidative stress. very good scavenger free radicals, itself also reduce stress binding thiol groups, decreasing their oxidation. potent inhibitor nitric oxide synthase. Increased levels shown cultures immune cells undergoing apoptosis. reminiscent staining neuronal perikarya dying after episode ischemia seizure activity. Thus possible role causing death needs fully investigated. intraventricular injections calcium EDTA already period ischemia. Pharmacological doses cause death, estimates indicate that extracellular could reach neurotoxic pathological conditions. high hippocampus during seizures. Unfortunately, there contrasting observations whether serves potentiate decrease additional least neurons damaged activity involved sprouting phenomenon give rise recurrent propagation hippocampus. Alzheimer's disease, has aggregate beta-amyloid, potentially neurotoxic. zinc-dependent factors NF-kappa B Sp1 bind promoter region amyloid precursor protein (APP) gene. inhibits degrade APP nonamyloidogenic peptides soluble beta-amyloid. changes occur neurological diseases implicated, such Parkinson's amyotrophic lateral sclerosis (ALS). superoxide dismutase 1, mutations familiar ALS. After HIV infection, deficiency found secondary immune-induced cytokine synthesis. replication virus sites. should stimulate further research neuropathology.