Zinc homeostasis and neurodegenerative disorders

Abstract

Zinc is an essential trace element, whose importance to the function of the central nervous system (CNS) is increasingly being appreciated. Alterations in zinc dyshomeostasis has been suggested as a key factor in the development of several neuropsychiatric disorders. In the CNS, zinc occurs in two forms: the first being tightly bound to proteins and, secondly, the free, cytoplasmic, or extracellular form found in presynaptic vesicles. Under normal conditions, zinc released from the synaptic vesicles modulates both ionotropic and metabotropic post-synaptic receptors. While under clinical conditions such as traumatic brain injury, stroke or epilepsy, the excess influx of zinc into neurons has been found to result in neurotoxicity and damage to postsynaptic neurons. On the other hand, a growing body of evidence suggests that a deficiency, rather than an excess, of zinc leads to an increased risk for the development of neurological disorders. Indeed, zinc deficiency has been shown to affect neurogenesis and increase neuronal apoptosis, which can lead to learning and memory deficits. Altered zinc homeostasis is also suggested as a risk factor for depression, Alzheimer's disease (AD), aging, and other neurodegenerative disorders. Under normal CNS physiology, homeostatic controls are put in place to avoid the accumulation of excess zinc or its deficiency. This cellular zinc homeostasis results from the actions of a coordinated regulation effected by different proteins involved in the uptake, excretion and intracellular storage/trafficking of zinc. These proteins include membranous transporters (ZnT and Zip) and metallothioneins (MT) which control intracellular zinc levels. Interestingly, alterations in ZnT and MT have been recently reported in both aging and AD. This paper provides an overview of both clinical and experimental evidence that implicates a dysfunction in zinc homeostasis in the pathophysiology of depression, AD, and aging.

The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism

“…Chronic perturbations of brain zinc homeostasis have been suggested to be closely related to the development of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS) (73, 104,392). The zinc levels (and other divalent cations) in the cerebrospinal fluid or in the brain of the patients are significantly altered (73,166,345,392).…”

Influence of Zinc Chloride Intragastric and Parenteral Administration on Systemic Hemodynamics in a Changing Calcium Homeostasis

“…Однако в некоторых состояниях, например, таких как ишемия, травмы ЦНС, деменция проис-ходит аккумуляция значительных количеств цинка в мозге, что вызывает токсические повреждения и гибель нейронов [10,13].…”

Oxidative Stress and Dietary Interventions in Autism: Exploring the Role of Zinc, Antioxidant Enzymes and Other Micronutrients in the Neurobiology of Autism

“…Zinc deficiency has been implicated in hyperactivity and jitters [46]. Children with autism have been shown to have lower zinc/copper ratios than normally developing peers and disturbed zinc homeostasis is suggested as a risk factor for neurodegenerative diseases [24,25,47].…”