Cholesterol and its reciprocal association with prion infection

Prion diseases are incurable, infectious and fatal neurodegenerative diseases that affect both humans and animals. The pathogenesis of prion disease involves the misfolding of the cellular prion protein, -PrPC, to a disease-causing conformation, -PrPSc, in the brain. The exact mechanism of conversion of -PrPC to -PrPSc is not clear; however, there are numerous studies supporting that this process of misfolding requires the association of -PrPC with lipid raft domains of the plasma membrane. An increase in the cellular cholesterol content with prion infection has been observed in both in vivo and in vitro studies. As cholesterol is critical for the formation of lipid rafts, on the one hand, this increase may be related to, or aiding in, the process of prion conversion. On the other hand, increased cholesterol levels may affect neuronal viability. Here, we discuss current literature on the underlying mechanisms and potential consequences of elevated neuronal cholesterol in prion infection and advancements in prion disease therapeutics targeting brain cholesterol homeostasis.

Automated summary

Prion diseases are incurable neurodegenerative diseases caused by the misfolding of cellular prion proteins. Studies suggest that the association of prion proteins with lipid rafts may play a role in this misfolding process. Prion infection leads to an increase in cellular cholesterol levels, which can potentially affect neuronal viability.