Trace elements and prion diseases: a review of the interactions of copper, manganese and zinc with the prion protein

Abstract

Transmissible spongiform encephalopathies (TSEs) are a family of neurodegenerative diseases characterized by their long incubation periods, progressive neurological changes, and spongiform appearance in the brain. There is much evidence to show that TSEs are caused by an isoform of the normal cellular surface prion protein PrPC. The normal function of PrPC is still unknown, but it exhibits properties of a cupro-protein, capable of binding up to six copper ions. There are two differing views on copper's role in prion diseases. While one view looks at the PrPC copper-binding as the trigger for conversion to PrPSc, the opposing viewpoint sees a lack of PrPC copper-binding resulting in the conformational change into the disease causing isoform. Manganese and zinc have been shown to interact with PrPC as well and have been found in abnormal levels in prion diseases. This review addresses the interaction between select trace elements and the PrPC.

A Case–Control Study on the Origin of Atypical Scrapie in Sheep, France

“…There is evidence suggesting that minerals, especially copper, manganese, and zinc, could play a role in the physiopathology of prion diseases (16,17). In contrast with our results, Hopp et al (15) found that feeding of vitamin and mineral supplements was associated with atypical scrapie.…”

“…In contrast with our results, Hopp et al (15) found that feeding of vitamin and mineral supplements was associated with atypical scrapie. The difference in the association between atypical scrapie and vitamin and mineral supplements in the 2 studies could be explained by differences in local conditions or roles of some minerals (17). Proper balance of minerals is complex because many interactions occur between mineral intake, diet of the animals, and physiologic conditions.…”

“…In 2006, a case-control study of atypical scrapie in Norway did not detect such factors, but it showed that the removal of the placenta at lambing could have a protective effect (15). Feeding of vitamin and mineral supplements showed an adverse effect, which was interpreted as interaction of some minerals with cellular prion protein (16,17), rather than a feed contamination. Such an effect warrants confi rmation.…”

Genetic analysis reveals polygenic influences on iron, copper, and zinc in mouse hippocampus with neurobiological implications

“…We found this worthy of mention because scrapie and other prion-related neurodegenerative diseases are also related to Cu homeostasis, in that prions are Cu-binding proteins. The role Cu plays in prion function, however, is not yet clear (Leach et al, 2006).…”

Carnosine: A Possible Drug for Vascular Dementia

“…The accumulation of Zn has also been observed following head trauma and epilepsy [59], implying that Zn neurotoxicity may underlie the pathological mechanisms of various injuries. Moreover, the disruption of Zn homeostasis has also been implicated in other neurodegenerative diseases, including AD [60][61][62], prion disease [63], amyotrophic lateral sclerosis [64], and Wilson's disease [65]. Thus, Zn may play a role like that of Janus, the ancient Roman god of doorways who has 2 different faces, in the brain: both Zn depletion and excess Zn cause severe damage to neurons.…”