Brain copper content and cuproenzyme activity do not vary with prion protein expression level

Area of Science:

• Neuroscience
• Biochemistry
• Molecular Biology

Background:

• Prion diseases stem from the misfolding of cellular prion protein (PrP(C)) into a pathogenic form (PrP(Sc)).
• PrP(C) binds copper ions, suggesting a role in brain copper metabolism, though its exact function remains unclear.

Purpose of the Study:

• To investigate the impact of varying prion protein (PrP) expression levels on brain copper content and cuproenzyme activity.
• To re-evaluate the proposed role of PrP(C) in copper metabolism.

Main Methods:

• Utilized transgenic mice expressing 0, 1, and 10 times the normal level of PrP.
• Employed mass spectrometry to quantify ionic copper in brain subcellular fractions.
• Assessed enzymatic activities of Cu-Zn superoxide dismutase and cytochrome c oxidase.
• Traced copper-64 ((64)Cu) incorporation into Cu-Zn superoxide dismutase in vitro and in vivo.

Main Results:

• No significant differences were observed in the amount of ionic copper within brain subcellular fractions across the different PrP expression levels.
• Enzymatic activities of Cu-Zn superoxide dismutase and cytochrome c oxidase remained consistent among the mouse lines.
• Copper-64 incorporation into Cu-Zn superoxide dismutase was similar in cultured neurons and in vivo, irrespective of PrP expression.

Conclusions:

• The level of PrP expression does not appear to influence brain copper levels or the activity of key cuproenzymes.
• These findings necessitate a reconsideration of the established role of PrP(C) in the regulation of brain copper metabolism.