Thallium Neurotoxicity: An Integrative Update

Ongoing investigation into the effects of thallium (Tl) on the central nervous system (CNS) yields new insights into the mechanisms underlying its toxicity. Tl is a heavy metal possessing specific chemical features that can induce severe acute and chronic intoxications in humans upon environmental, occupational, accidental, and intentional exposures, with adverse effects in all organs, and particularly the brain. It readily crosses the blood-brain barrier (BBB) and triggers a series of cellular, molecular, and biochemical events, leading to alterations at the central level that compromise cognitive and motor functions. Experimental studies have shown that Tl alters intracellular redox status to induce oxidative damage, mitochondrial dysfunction, apoptotic cell signaling, and major motor changes. In this review we update, in an integrative manner, the mechanisms of Tl toxicity at several functional levels. This state-of-the-art review compiles and discusses recent and past evidence to integrate a general toxic scheme to explain Tl’s neurotoxic effects, identifying effective therapeutic approaches against the neurological sequelae of Tl exposure. The review also describes the use of Tl in nanoparticles for several industrial and pharmacological processes, highlighting it as a potential source of human exposure. Combined, the evidence reviewed in this document led us to suggest an integrative mechanistic hypothesis on the toxic effects of Tl.