Neuroprotective effect and potential of cellular prion protein and its cleavage products for treatment of neurodegenerative disorders part I. a literature review

Prion Protein: The Molecule of Many Forms and Faces

“…It is anchored to the cell membrane with a glycosylphosphatidylinositol (GPI) anchor [21,22]. The flexible N-terminal domain contains an octarepeat region whereas the structured domain consists of three α-helices, two β-sheets, a disulfide bond connecting cysteines 179 and 214 and two N-glycans on amino acid residues 181 and 197 [23,24] (Figure 1). structured domain consists of three α-helices, two β-sheets, a disulfide bond connecting cysteines 179 and 214 and two N-glycans on amino acid residues 181 and 197 [23,24] (Figure 1).…”

“…The flexible N-terminal domain contains an octarepeat region whereas the structured domain consists of three α-helices, two β-sheets, a disulfide bond connecting cysteines 179 and 214 and two N-glycans on amino acid residues 181 and 197 [23,24] (Figure 1). structured domain consists of three α-helices, two β-sheets, a disulfide bond connecting cysteines 179 and 214 and two N-glycans on amino acid residues 181 and 197 [23,24] (Figure 1). PrP C can transform into a β-sheet-rich isoform PrP Sc , which is prone to autocatalytic conversion and aggregation into insoluble aggregates [22,25,26].…”

“…The cleavage releases an ~11 kDa fragment N1 whereas the ~18 kDa part C1 remains attached to the cell membrane by the GPI anchor [36,39]. For now, there is no unique enzyme responsible for the α-cleavage [24,40]. Although cleavage sites have been determined with respect to species, the α-cleavage is tolerant to sequence variation in this region as long as its hydrophobicity remains preserved [38].…”

“…Similar to the α-cleavage, the shedding of PrP occurs in the presence of enzymes from the ADAM family. In vitro and in vivo experiments suggest that ADAM9 and ADAM10 are involved in the process of cleavage and the shedding of PrP [47,[84][85][86] where ADAM10 is the primary sheddase for PrP and ADAM9 is the modulator of ADAM10 activity [24]. Shed PrP was first determined in hamsters.…”

“…Neurodegeneration occurs in diseases such as prion disease, PD and AD due to the aggregation of PrP Sc [26,172,173], α-syn [174][175][176][177] and Aβ isoforms [178,179] and tau protein [180][181][182][183], respectively. Prion protein or prion protein fragments have been found to interact with aggregating agents in different neurodegenerative diseases but their roles depend on the studied conditions [24,81,184,185].…”