The highways and byways of prion protein trafficking

Campana, Vincenza; Sarnataro, Daniela; Zurzolo, Chiara

doi:10.1016/j.tcb.2004.12.002

Cited by 160 publications

(152 citation statements)

References 79 publications

Supporting

Mentioning

144

Contrasting

Unclassified

Order By: Relevance

“…16,17 Increasing evidence suggests that events taking place in these compartments play a modulating role in the pathogenesis of several neurodegenerative disorders. 18 In line with these observations, recent studies 15,19 implicated the potential role of association with endoplasmic reticulum (ER) lipid raft-like microdomains for a correct folding of PrP C , as well as for the export of the protein to the Golgi and proper glycosylation, 20 suggesting a quality control mechanism for ER raft-like microdomains in distribution of mature PrP C among cellular compartments and distinct regions of the plasma membrane. Immature and misfolded proteins are normally retained in ER and subject to the ER-associated degradation pathway.…”

Section: The Role Of Cellular Prion Protein In Cell Activationmentioning

confidence: 73%

Trafficking of PrP^cto mitochondrial raft-like microdomains during cell apoptosis

Sorice

Mattei

Tasciotti

et al. 2012

Prion

View full text Add to dashboard Cite

Section: The Role Of Cellular Prion Protein In Cell Activationmentioning

confidence: 73%

Trafficking of PrP^cto mitochondrial raft-like microdomains during cell apoptosis

Sorice

Mattei

Tasciotti

et al. 2012

Prion

View full text Add to dashboard Cite

“…Unlike most neurodegenerative proteins that produce cytosolic aggregates susceptible to clearance by rapamycin-induced macroautophagy, PrP is a GPI-anchored protein that follows the secretory pathway to the plasma membrane (Campana et al, 2005). Plaques in Tg(PrP-A116V) mice appear to be comprised of full-length PrP-A116V molecules (Yang et al, 2009), suggesting it is cleaved from the plasma membrane at the GPI anchor, or secreted, as in PrP(GPI-) mice (Chesebro et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Rapamycin Delays Disease Onset and Prevents PrP Plaque Deposition in a Mouse Model of Gerstmann–Sträussler–Scheinker Disease

et al. 2012

View full text Add to dashboard Cite

Autophagy is a cell survival response to nutrient deprivation that delivers cellular components to lysosomes for digestion. In recent years, autophagy has also been shown to assist in the degradation of misfolded proteins linked to neurodegenerative disease (Ross and Poirier, 2004). In support of this, rapamycin, an autophagy inducer, improves the phenotype of several animal models of neurodegenerative disease. Our Tg(PrP-A116V) mice model Gerstmann-Sträussler-Scheinker disease (GSS), a genetic prion disease characterized by prominent ataxia and extracellular PrP amyloid plaque deposits in brain (Yang et al., 2009). To determine whether autophagy induction can mitigate the development of GSS, Tg(PrP-A116V) mice were chronically treated with 10 or 20 mg/kg rapamycin intraperitoneally thrice weekly, beginning at 6 weeks of age. We observed a dose-related delay in disease onset, a reduction in symptom severity, and an extension of survival in rapamycin-treated Tg(PrP-A116V) mice. Coincident with this response was an increase in the autophagy-specific marker LC3II, a reduction in insoluble PrP-A116V, and a near-complete absence of PrP amyloid plaques in the brain. An increase in glial cell apoptosis of unclear significance was also detected. These findings suggest autophagy induction enhances elimination of misfolded PrP before its accumulation in plaques. Because ataxia persisted in these mice despite the absence of plaque deposits, our findings also suggest that PrP plaque pathology, a histopathological marker for the diagnosis of GSS, is not essential for the GSS phenotype.

show abstract

“…The question arises, however, of whether and how such a scenario could apply to PrP Sc , of which the known deposition sites are the cell surface or the endocytic compartment, where the conversion process may take place (Campana et al, 2005). It should be pointed out that our findings overall are in good accordance with those of Kristiansen et al (2005), who reported the formation of PrP Sc -containing aggresome-like structures in N2a and GT1 cell cultures subjected to a mild treatment by lactacystin.…”

Section: Discussionmentioning

confidence: 99%

Proteasome inhibitors promote the sequestration of PrPSc into aggresomes within the cytosol of prion-infected CAD neuronal cells

Dron

Dandoy-Dron

Salamat

et al. 2009

Journal of General Virology

View full text Add to dashboard Cite

Dysfunction of the endoplasmic reticulum associated protein degradation/proteasome system is believed to contribute to the initiation or aggravation of neurodegenerative disorders associated with protein misfolding, and there is some evidence to suggest that proteasome dysfunctions might be implicated in prion disease. This study investigated the effect of proteasome inhibitors on the biogenesis of both the cellular (PrPC) and abnormal (PrPSc) forms of prion protein in CAD neuronal cells, a newly introduced prion cell system. In uninfected cells, proteasome impairment altered the intracellular distribution of PrPC, leading to a strong accumulation in the Golgi apparatus. Moreover, a detergent-insoluble and weakly protease-resistant PrP species of 26 kDa, termed PrP26K, accumulated in the cells, whether they were prion-infected or not. However, no evidence was found that, in infected cells, this PrP26K species converts into the highly proteinase K-resistant PrPSc. In the infected cultures, proteasome inhibition caused an increased intracellular aggregation of PrPSc that was deposited into large aggresomes. These findings strengthen the view that, in neuronal cells expressing wild-type PrPC from the natural promoter, proteasomal impairment may affect both the process of PrPC biosynthesis and the subcellular sites of PrPSc accumulation, despite the fact that these two effects could essentially be disconnected.

show abstract

The highways and byways of prion protein trafficking

Cited by 160 publications

References 79 publications

Trafficking of PrP^cto mitochondrial raft-like microdomains during cell apoptosis

Trafficking of PrP^cto mitochondrial raft-like microdomains during cell apoptosis

Rapamycin Delays Disease Onset and Prevents PrP Plaque Deposition in a Mouse Model of Gerstmann–Sträussler–Scheinker Disease

Proteasome inhibitors promote the sequestration of PrPSc into aggresomes within the cytosol of prion-infected CAD neuronal cells

Contact Info

Product

Resources

About

The highways and byways of prion protein trafficking

Cited by 160 publications

References 79 publications

Trafficking of PrPcto mitochondrial raft-like microdomains during cell apoptosis

Trafficking of PrPcto mitochondrial raft-like microdomains during cell apoptosis

Rapamycin Delays Disease Onset and Prevents PrP Plaque Deposition in a Mouse Model of Gerstmann–Sträussler–Scheinker Disease

Proteasome inhibitors promote the sequestration of PrPSc into aggresomes within the cytosol of prion-infected CAD neuronal cells

Contact Info

Product

Resources

About

Trafficking of PrP^cto mitochondrial raft-like microdomains during cell apoptosis

Trafficking of PrP^cto mitochondrial raft-like microdomains during cell apoptosis