Intracellular zinc liberation: A trigger for oxidative stress-induced toxicity to neurons and neuroglia

Oxidative and nitrosative stress is a common feature in the initiation and propagation of many neurological and neurodegenerative diseases. Although multiple and distinct signaling cascades are involved in the toxicity of various neural cells, increasing evidence suggests that intracellular zinc liberation is an early initiator and trigger for the subsequent cell death pathways. Activation of protein kinase c (PKC) and mitogen-activated protein kinase (MAPK) by intracellularly released zinc not only contributes to the toxicity of neurons, but also to the toxicity of neuroglia, including oligodendrocytes, astrocytes, and microglia. Therefore, maintenance of the intracellular zinc homeostasis and targeting the downstream signaling molecules may provide therapeutic strategies for the treatment of neurological disorders, in which multiple neural cells may be involved and injured under stressful and pathological conditions.