Aluminium and lead: molecular mechanisms of brain toxicity
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The fact that aluminium (Al) and lead (Pb) are both toxic metals to living organisms, including human beings, was discovered a long time ago. Even when Al and Pb can reach and accumulate in almost every organ in the human body, the central nervous system is a particular target of the deleterious effects of both metals. Select human population can be at risk of Al neurotoxicity, and Al is proposed to be involved in the etiology of neurodegenerative diseases. Pb is a widespread environmental hazard, and the neurotoxic effects of Pb are a major public health concern. In spite of the numerous efforts and the accumulating evidence in this area of research, the mechanisms of Al and Pb neurotoxicity are still not completely elucidated. This review will particularly address the involvement of oxidative stress, membrane biophysics alterations, deregulation of cell signaling, and the impairment of neurotransmission as key aspects involved Al and Pb neurotoxicity.
KeywordsAluminium Lead Neurotransmission Oxidative stress Neurotoxicity Cell signaling Calcium Toxicology
This work has been supported by grants from the University of Buenos Aires, Fundación Antorchas, and CONICET, Argentina, and by grants from the National Institute of Environmental Health Services Center for Environmental Health Sciences, University of California, Davis, and from the University of California, Davis. P.I.O. is a member (Investigador correspondiente) of CONICET, Argentina. S.V.V. is a career investigator of CONICET, Argentina.
- DC C (2000) Blood lead levels in young children—United States and selected states, 1996–1999. MMWR Morb Mortal Wkly Rep 49:1133–1137Google Scholar
- Klaassen CD (2001) Heavy metals and heavy-metal antagonists. In: Hardman JG, Limbird LE, Goodman Gilman A (eds) The pharmacological basis of therapeutics. McGraw Hill, New York, pp 1851–1875Google Scholar
- Magyar JS, Weng TC, Stern CM, Dye DF, Rous BW, Payne JC, Bridgewater BM, Mijovilovich A, Parkin G, Zaleski JM, Penner-Hahn JE, Godwin HA (2005) Reexamination of lead(II) coordination preferences in sulfur-rich sites: implications for a critical mechanism of lead poisoning. J Am Chem Soc 127:9495–9505PubMedGoogle Scholar
- Mendez-Alvarez E, Soto-Otero R, Hermida-Ameijeiras A, Lopez-Real AM, Labandeira-Garcia JL (2002) Effects of aluminum and zinc on the oxidative stress caused by 6-hydroxydopamine autoxidation: relevance for the pathogenesis of Parkinson’s disease. Biochim Biophys Acta 1586:155–168PubMedGoogle Scholar
- Sies H, Jones D (2007) Oxidative Stress. In: Fink G (ed) Encyclopedia of stress. Elsevier, San Diego, pp 45–48Google Scholar
- Verstraeten SV (2000) Mechanisms involved in the oxidative damage to membranes mediated by aluminum and aluminum-related cations. Effects in vitro and in vivo. In: School of Pharmacy and Biochemistry. University of Buenos Aires, Buenos Aires, ArgentinaGoogle Scholar