Biometals in rare neurodegenerative disorders of childhood

Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland Kuopio, Finland.
Frontiers in Aging Neuroscience (Impact Factor: 4). 03/2013; 5:14. DOI: 10.3389/fnagi.2013.00014
Source: PubMed


Copper, iron, and zinc are just three of the main biometals critical for correct functioning of the central nervous system (CNS). They have diverse roles in many functional processes including but not limited to enzyme catalysis, protein stabilization, and energy production. The range of metal concentrations within the body is tightly regulated and when the balance is perturbed, debilitating effects ensue. Homeostasis of brain biometals is mainly controlled by various metal transporters and metal sequestering proteins. The biological roles of biometals are vastly reviewed in the literature with a large focus on the connection to neurological conditions associated with ageing. Biometals are also implicated in a variety of debilitating inherited childhood disorders, some of which arise soon following birth or as the child progresses into early adulthood. This review acts to highlight what we know about biometals in childhood neurological disorders such as Wilson's disease (WD), Menkes disease (MD), neuronal ceroid lipofuscinoses (NCLs), and neurodegeneration with brain iron accumulation (NBIA). Also discussed are some of the animal models available to determine the pathological mechanisms in these childhood disorders, which we hope will aid in our understanding of the role of biometals in disease and in attaining possible therapeutics in the future.

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    • "They have a key role in many rarer forms of neurodegeneration including childhood neurodegenerative disorders. Parker et al. (2013), report on the role of metals in neuronal ceroid lipofuscinosis, neurodegeneration with brain iron accumulation (NBIA), and additional diseases, further extending the links between genetic mutations and metal abnormalities in these disorders. Obviously, while this is a rapidly expanding field of research, as illustrated here, we still have much further to go to achieve a major understanding of where these biometal changes fit into the neurodegenerative disease process. "

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    ABSTRACT: Neurodegenerative disorders are featured by a variety of pathological conditions that share similar critical processes, such as oxidative stress, free radical activity, proteinaceous aggregations, mitochondrial dysfunctions, and energy failure. They are mediated or triggered by an imbalance of metal ions leading to changes of critical biological systems and initiating a cascade of events finally leading to neurodegeneration and cell death. Their causes are multifactorial, and although the source of the shift in oxidative homeostasis is still unclear, current evidence points to changes in the balance of redox transition metals, especially iron, copper, and other trace metals. They are present at elevated levels in Alzheimer disease, Parkinson disease, multisystem atrophy, etc., while in other neurodegenerative disorders, copper, zinc, aluminum, and manganese are involved. This chapter will review the recent advances of the role of metals in the pathogenesis and pathophysiology of major neurodegenerative diseases and discuss the use of chelating agents as potential therapies for metal-related disorders.
    No preview · Article · Nov 2013 · International Review of Neurobiology
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