Heparan sulfate chains have been found to be associated with amyloid deposits in a number of diseases including transmissible spongiform encephalopathies. Diverse lines of evidence have linked proteoglycans and their glycosaminoglycan chains, and especially heparan sulfate, to the metabolism of the prion protein isoforms. Glypicans are a family of glycosylphosphatidylinositol-anchored, heparan ...

Prions normally exist as cellular membrane proteins. In humans, 209 amino acids with one disulfide bond form a primarily alpha-helical prion protein structure with a molecular mass of 35 to 36 kDa. The specific role and function of the prion protein elude research efforts and remains a controversial topic. Misfolding of the native prion protein leads to a protein structure with increased propor...

Neurodegenerative disorders are characterized by synaptic and neuronal dysfunction which precedes general neuronal loss and subsequent cognitive or behavioral anomalies. Although the exact early cellular signaling mechanisms involved in neurodegenerative diseases are largely unknown, a view is emerging that compromised synaptic function may underlie the initial steps in disease progression. Muc...

Bovine spongiform encephalopathy (BSE) is a fatal infectious neurodegenerative disease in cattle, characterized by the accumulation of an abnormal, proteaseresistant prion protein (PrPSc) in the brain. BSE is similar to scrapie in sheep and goats and Creuzfeldt-Jakob disease in humans. Susceptibility in cattle hasbeen shown to be under the influence of two polymorphic locations, which are...

Two protein-based genetic elements (prions) have been identified in yeast. It is not clear whether other prions exist, nor is it understood how one might find them. We established criteria for searching protein databases for prion candidates and found several. The first examined, Rnq1, exists in distinct, heritable physical states, soluble and insoluble. The insoluble state is dominant and tran...

Prion proteins have the unusual capacity to fold into two functionally distinct conformations, one of which is self-perpetuating. When yeast prion proteins switch state, they produce heritable phenotypes. We report prion-like properties in a neuronal member of the CPEB family (cytoplasmic polyadenylation element binding protein), which regulates mRNA translation. Compared to other CPEB family m...

Prion diseases are neurodegenerative disorders characterized by the aggregation of abnormally folded prion protein (PrP(Sc)). In this study, we focused on the mechanism of clearance of PrP(Sc), which remains unclear. p62 is a cytosolic protein known to mediate both the formation and degradation of aggregates of abnormal proteins. The levels of p62 protein increased in prion-infected brains and ...

Exosomes are involved in the progression of neurodegenerative diseases. The cellular prion protein (PrPC) is highly expressed on exosomes. In neurodegenerative diseases, PrPC has at least two functions: It is the substrate for the generation of pathological prion protein (PrPSc), a key player in the pathophysiology of prion diseases. On the other hand, it binds neurotoxic amyloid-beta (Aß) olig...