Biometal dyshomeostasis and toxic metal accumulation are common features in many neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease and Huntington’s disease. The neurotoxic effects of metal imbalance are generally associated with reduced enzymatic activities, elevated protein aggregation and oxidative stress in the central nervous system, in which a cascade of events lead to cell death and neurodegeneration. Although the links between biometal imbalance and neurodegenerative disorders remain elusive, a major class of endogenous proteins involved in metal transport has been receiving increasing attention over recent decades. The abnormal expression of these proteins has been linked to biometal imbalance and to the pathogenesis of AD. Here, we present a brief overview of the physiological roles of biometals including iron, zinc, copper, manganese, magnesium and calcium, and provide a detailed description of their transporters and their synergistic involvement in the development of AD. In addition, we also review the published data relating to neurotoxic metals in AD, including aluminum, lead, cadmium and mercury.

It is now increasingly appreciated that glial cells play a critical role in the regulation of iron homeostasis. Impairment of these properties might lead to dysfunction of iron metabolism and neurodegeneration of neurons. We have previously shown that dysfunction of glia could cause iron deposit and enhance iron-induced degeneration of dopamine (DA) neurons in Parkinson’s disease (PD). There also has been a substantial growth of knowledge regarding the iron metabolism of glia and their effects on iron accumulation and degeneration of DA neurons in PD in recent years. Here, we attempt to describe the role of iron metabolism of glia and the effect of glia on iron accumulation and degeneration of DA neurons in the substantia nigra of PD. This could provide evidence to reveal the mechanisms underlying nigral iron accumulation of DA neurons in PD and provide the basis for discovering new potential therapeutic targets for PD.