The normal cellular prion protein (PrP^C) may play a significant role in slowing down the formation of protein aggregates in Huntington's Disease and Alzheimer's Disease, new scientific evidence suggests. This new data will have implications for therapeutic strategies aimed at slowing down prion formation by the depletion of PrP^C.

Although a lot is known about the normal cellular prion protein (PrP^C) as a precursor of the aberrant folded PrPS^c in prion disease, its normal cellular function remains unclear. Its influence on important cellular processes such as cell survival has been suggested. New evidence suggests that PrP^C may play a significant role in the prevention of both Huntington's Disease and Alzheimer's Disease.

Deposition of insoluble aggregates
The key pathogenic events that are shared between these diseases and prion diseases include the deposition and aggregation of insoluble, aberrantly formed proteins. In Alzheimer's Disease, amyloid beta protein is produced from the amyloid precursor protein (APP), which aggregates to form plaques and is associated with neurodegeneration. In Huntington's disease, a longer than normal sequence of poly glutamine amino acids in the Huntington protein leads to the formation of protein aggregates. The higher the number of glutamine residues, the earlier the onset of the disease. In vitro experiments by Parkin et al. and Lee and colleagues have shown that it is the presence of PrP^C that prevents the formation of these protein aggregates. Moreover, Lee et al. show that PrP^C specifically increases proteosome activity in neuronal cells, which protects the cells against protein aggregates. They suggest that PrP^C may also play a protective role against other neurodegenerative diseases.

Consequences for prion therapeutics
What are the consequences of these findings? One of the implications is that caution should be taken in the development of therapeutics for prion diseases. For example, the depletion of PrP^C as a treatment to stop the progression of a disease, may trigger other neurodegenerative diseases.