MOLECULAR MECHANISMS OF LEAD NEUROTOXICITY.

Abstract

Lead (Pb²⁺) is a non-essential metal with numerous industrial applications that have led to ts ubiquity in the environment. Thus, not only occupational-exposed individuals' health is compromised, but also that of the general population and in particular children. Notably, although the central nervous system is particularly susceptible to Pb²⁺, other systems are affected as well. The present study focuses on molecular mechanisms that underlie the effects that arise from the presence of Pb²⁺ in situ in the brain, and the possible toxic effects that follows. As the brain barriers represent the first target of systemic Pb²⁺, mechanisms of Pb²⁺ entry into the brain are discussed, followed by a detailed discussion on neurotoxic mechanisms, with special emphasis on theories of ion mimicry, mitochondrial dysfunction, redox imbalance, and neuroinflammation. Most importantly, the confluence and crosstalk between these events is combined into a cogent mechanism of toxicity, by intertwining recent and old evidences from humans, in vitro cell culture and experimental animals. Finally, pharmacological interventions, including chelators, antioxidants substances, anti-inflammatory drugs, or their combination are reviewed as integrated approaches to ameliorate Pb²⁺ harmful effects in both developing or adult organisms.