Abstract
Cellular (also termed ‘natural’) prion protein has been extensively studied for many years for its pathogenic role in prionopathies after misfolding. However, neuroprotective properties of the protein have been demonstrated under various scenarios. In this line, the involvement of the cellular prion protein in neurodegenerative diseases other than prionopathies continues to be widely debated by the scientific community. In fact, studies on knock-out mice show a vast range of physiological functions for the protein that can be supported by its ability as a cell surface scaffold protein. In this review, we first summarize the most commonly described roles of cellular prion protein in neuroprotection, including antioxidant and antiapoptotic activities and modulation of glutamate receptors. Second, in light of recently described interaction between cellular prion protein and some amyloid misfolded proteins, we will also discuss the molecular mechanisms potentially involved in protection against neurodegeneration in pathologies such as Alzheimer’s, Parkinson’s, and Huntington’s diseases.
Highlights
Pathogenic conformational changes of cellular prion protein (PrPC ) generates a β-sheet-enriched isoform called PrPSc or prion [1,2,3], the causal agent of prionopathies [1,2]
It is important to keep in mind that the activity of PrPC is finely regulated by its dimerization and that PrPC homodimers stimulate the production of PrPN1, which in turn can bind to Aβ with high affinity, blocking transformation into soluble and toxic Aβ-derived diffusible ligands (ADDLs) [136,160,161,164]
We argue for the role of PrPC in preventing the detrimental effects of the oligomeric species, especially at early stages of the neurodegenerative processes
Summary
Pathogenic conformational changes of cellular prion protein (PrPC ) generates a β-sheet-enriched isoform called PrPSc or prion (word derived from proteinaceous infectious particle) [1,2,3], the causal agent of prionopathies [1,2]. C in [51,52] In this respect, conflicting studies report neurotoxic rolestissue of PrP particular In. Aβ (red) in others point to a neuroprotective function of the protein in the same disease (i.e., AD), discussed the postmortem frontal cortex of an patient in contrast to other prion-like below. Proteins such as α-synuclein with little colocalization with Aβ-positive the sameproteins, context; In the present review, far from arguing the pathogenicity of PrPSc plaques or otherin prion-like normal endogenous expression function of PrP be largely compromised. Far from arguing the pathogenicity of PrPSc or other prion-like proteins, which has already been done in several reviews (see, for instance, [53,54,55,56]), we will focus our attention on the neuroprotective role of PrPC and its putative implication in amyloid-associated NDDs
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