Prion Protein and Wilson’s disease

Introduction

Wilson’s disease (WD), a human autosomal recessive disorder caused by mutations in the copper-transporting ATP7B gene, has been classified into hepatic, neurologic, psychiatric and asymptomatic phenotypes, differently regulated by molecular and epigenetic mechanisms, the main area of research thus far. Despite the recognized affinity of prion protein (PrP) with copper and the impact of prion gene polymorphism on the course of this disease, few reports have questioned the relation between PrP and WD.

Objectives

A recent publication, based on in vitro and in vivo models, reported that cellular PrP (PrP^c) promotes copper toxicity in WD hepatocytes. These results led us to test the presence of PrP^c in the lesions (striatum and pons) of WD patients.

Methods

We performed immunohistochemistry on formol-fixed, paraffin-embedded, archived fragments from 3 patients:   Case 1 aged 19 (neurologic), Case 2 aged 30 (psychiatric). Case 3 aged 65 (classic), respectively treated by penicillamine for 8-9 months and 24 years and controls.

Results

IHC results revealed

• strong cellular PrP^c labelling of striatal (cases 1 & 2), pontine (case 2) spongio-necrotic foci, absent in case 3.
• Mild labeling of an original hemispheric white matter lesion (case 2)
• No labelling of normal tissue (patients and controls)
• PrP^c labelling of control central pontine myelinolysis.

Discussion/Conclusion.

Our end-staged results clearly highlight an inference of the cellular prion protein in these neuropathological processes. However, since PrP^c is known to be a dual agent, the particular role(s) of PrP^c in the neurological aspects of WD will be discussed.