Manganese efflux in Parkinsonism: insights from newly characterized SLC30A10 mutations

Abstract

Although manganese (Mn) is required for normal cellular function, overexposure to this metal may cause an extrapyramidal syndrome resembling Parkinson's disease (PD). Notably, high whole-blood Mn levels have been reported in patients with idiopathic PD. Because Mn is both essential at low dose and toxic at higher dose; its transport and homeostasis are tightly regulated. Previously, the only protein known to be operant in cellular Mn export was the iron-regulating transporter, ferroportin (Fpn). The causal role for Mn in PD has yet to be fully understood, but evidence of a familial predisposition to PD associated with Mn toxicity is mounting. A recently discovered mutation in SLC30A10 identified its gene product as putatively involved in Mn efflux. Patients with the SLC30A10 mutation display Parkinsonian-like gate disturbances and hypermanganesemia. This review will address Mn transport proteins, the newly discovered SLC30A10 mutations and their implications to Parkinsonism and Mn regulation.