Manganese in health and disease

Abstract

Manganese is an important metal for human health, being absolutely necessary for development, metabolism, and the antioxidant system. Nevertheless, excessive exposure or intake may lead to a condition known as manganism, a neurodegenerative disorder that causes dopaminergic neuronal death and parkinsonian-like symptoms. Hence, Mn has a paradoxal effect in animals, a Janus-faced metal. Extensive work has been carried out to understand Mn-induced neurotoxicity and to find an effective treatment. This review focuses on the requirement for Mn in human health as well as the diseases associated with excessive exposure to this metal.

Figure 1

Mechanism of Mn transport across the BBB under physiological Mn exposure levels. Transporters and relevant manganese oxidation states associated with Mn transport are demonstrated. Mn bound to albumin is excluded from passing the BBB given its size. Arrow size depicts the relative importance of each of the transporters in this process, bolder arrows representing more prominent transport mechanisms. Please refer to the discussion for additional details. Since it has yet to be determined whether ZIP8 functions to transport Mn across the BBB, the process has been annotated with a question mark.

Figure 2

Identified and putative Mn transporters. These illustrated Mn transporters have been demonstrated to facilitate Mn trafficking (uptake, storage, efflux) between the extra- and intracellular milieu. Each of these transporter proteins has also been implicated in the transport of other metals.