Impairment of Erythropoiesis In Inbred Cellular Prion Protein Deficient Mice.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2032-2032
Author(s):  
Hana Glierova ◽  
Martin Panigaj ◽  
Jana Semberova ◽  
Olga Janouskova ◽  
Eva Dvorakova ◽  
...  
Keyword(s):  
Prion Protein ◽  
Mouse Models ◽  
Blood Cells ◽  
Prion Diseases ◽  
Cellular Prion Protein ◽  
Erythroid Cell ◽  
Hematopoietic Stem ◽  
Acute Anemia ◽  
The Difference

Abstract Abstract 2032 Cellular prion protein (PrPc) plays a key role in pathogenesis of prion diseases, however, its physiologic function remains unclear. The involvement of PrPc in hematopoiesis was suggested by importance of its expression for self renewal and survival of long term repopulating hematopoietic stem cells. Prion diseases were shown to deregulate transcription of several erythroid genes and we have demonstrated reduction of erythroid cell and erythropoietin production in FVB PrP-/- (Zurich I) mice in response to acute anemia (Zivny J. et al. Blood Cells Mol Dis. 2008;40:302-307). In this study, we exploited different mouse models with manipulated level of PrPc expression to verify the role of PrPc in erythropoiesis. First set of experiments was carried out on PrP-/- (Zurich I) and Tga20 PrP over-expressing mice on a mixed C57Bl6/129Sv genetic background. Inbred C57Bl6 mice served as a wild type control (WT). Induction of acute anemia by phenylhydrazine (PHZ) in PrP-/- and WT mice (n=18) led to drop in the hematocrit (HCT) from 52.5±1.5 and 49.8±2.5% to 37.9± 1.0 and 41.9±3.0% after 24 h, respectively. The course of anemia was significantly deeper in PrP-/- mice at 72 h, 96 h and 120 h (p < 0.01) after PHZ administration. Plasma levels of erythropoietin (Epo) in response to anemia reached higher maximum levels in PrP-/- than WT mice (2250 vs. 1810 pg/mL) although rose more slowly. The level of Epo mRNA in kidneys increased approximately 30-fold in both, WT and PrP-/- mice, however, in WT mice peaked at 24 h whereas in KO mice at 96 h. We repeated the study with smaller groups of PrP-/- and Tga20 mice (n=9) and analysed samples 24 h and 96 h post anemia induction. Random PrP gene re-introduction in Tga20 mice rescued the animals from severe anemia. Decrease in HCT after PHZ administration was significantly lower in Tga20 comparing to PrP-/- mice and was accompanied by less elevated reticulocyte (RTC) count, plasma Epo level and level of Epo mRNA in kidneys. Next we studied the dynamics of unchallenged erythropoiesis in PrP-/-, Tga20 and WT mice by in vivo labelling of blood cells with NHS-biotin and subsequent flow cytometric analysis of relative numbers of newly produced non-labelled RBC. WT mice had significantly enhanced turnover of RBC with higher counts of non-labelled RBC comparing to PrP-/- during 46 days of chase (p < 0.05). Half- life of labeled RBC in WT mice was 20 days, but 32 and 30 days in PrP-/- and Tga20 mice, respectively. Tga20 mice displayed tendency to increased RBC turnover over PrP-/- mice, but the difference was significant only 2 and 33 days after initiation of the experiment. Having in mind possible limitations of experiments conducted in genetically modified inbred mice we have designed second set of experiments in more stringent animal models. We mated C57Bl6/129Sv PrP-/- mice with inbred C57Bl6 and outbred CD-1 mice. Heterozygotes in F1 generation were mated and their PrP -/-, PrP -/+ and PrP +/+ offspring used in the experiments. Anemia was induced by PHZ and blood was sampled from tail vein at defined time points and HCT and RTC count were analysed. In C57Bl6 crossbreeds we observed significantly higher starting HCT level in PrP-/- mice (p < 0.05) compared to PrP-/+ and PrP+/+ mice reaching 53.2±2.3, 50.0±2.1 and 49±2.9%, respectively. Similar decrease in HCT was observed for all PrP groups 24 h after PHZ administration, however, significant differences between PrP-/- and PrP+/+ mice were recorded at 48 h and 72 h. The recovery to normal HCT was again retarded in PrP-/- mice. RTC counts rose more rapidly in PrP+/+ mice after PHZ administration and declined to basal levels faster than in PrP-/- mice, the difference reached significance at 24 h, 48 h and 96 h. Dynamics of unchallenged erythropoiesis in C57Bl6 crossbreeds was similar in all three PrP genotypes with no significant differences in numbers of newly produced RBC during 57 days of the experiment. In CD-1 crossbreed mice no significant differences in HCT and RTC counts were detected after PHZ induced anemia among PrP-/-, PrP-/+ and PrP+/+ siblings. Also the dynamics of unchallenged erythropoiesis was similar in all PrP genotypes. To sum up, our data confirmed the role of PrPc in stress erythropoiesis in studied inbred mouse models. In outbred model the effect of PrP deletion on erythropoiesis seems to be compensated. (GACR310/08/0878, GAUK86408) Disclosures: No relevant conflicts of interest to declare.

The Post-Transfusion Recovery and Survival of Red Blood Cells in Mice Is Affected by the Expression of Cellular Prion Protein.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 959-959
Author(s):  
Karel Holada ◽  
Jan Simak ◽  
Jaroslav G. Vostal
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Red Blood Cells ◽  
Prion Protein ◽  
Blood Cells ◽  
Survival Curve ◽  
Protective Role ◽  
Cellular Prion Protein ◽  
Hematopoietic Stem

Abstract Three documented transfusion cases of vCJD underline the need of better insight in blood prion protein biology. Cellular prion protein (PrPc) plays key role in the pathophysiology of prion diseases. Its expression by cells is necessary for amplification of infectious prions and the disease process itself. Physiological function of PrPc remains obscure. Its clarification may provide important clues for the development of urgently needed blood test and effective disease treatment. PrPc is expressed on CD34+ hematopoietic stem cells and its expression is regulated during blood cell differentiation. Recently the importance of PrPc for self-renewal of long-term repopulating hematopoietic stem cells was suggested and other studies reported the protective function of PrPc against oxidative stress and apoptosis in various cell cultures. We previously demonstrated that human as well as mouse red blood cells (RBC) express approximately 200 PrPc molecules / cell (Holada et al., BJH 2000, 110, 472–80). To test if the PrPc expression plays a role in the post-transfusion recovery and survival of RBC we carried out transfusion study in mice. RBC isolated from blood of wild type (WT) and PrP knockout (KO) FVB mice were labeled “in vitro” by different levels of NHS-biotin. The labeling was optimized to allow simultaneous detection of both populations of RBC in mouse blood using flow cytometry. To exclude the influence of different level of cell biotinylation on the experiment outcome two mixtures of RBC were prepared. The first contained KO RBC labeled with high and WT RBC with low level of biotin and the second mixture contained cells labeled “vice versa”. Each mixture was injected via tail vein in a group of WT mice (n=5) and the survival of RBCs was followed. Samples were analyzed on day 1, 2, 3, 6, 9, 15, 21 and 29. The count of biotinylated RBC was measured in comparison to 100 000 nonlabeled recipient RBC. Simultaneously the expression of PrPc on RBC was monitored using flow cytometry with MAb 6H4. KO RBC displayed significantly higher first day post-transfusion recovery compared to WT RBC in both groups of mice (81 ± 3 % vs. 74 ± 3 %, P&lt;0.005 and 90 ± 4 % vs. 80 ± 4 %, P&lt;0.005). The slope of the RBC survival curve in all individual mice during the initial 15 days was steeper for KO RBC (mavg = − 3.44) than for WT RBC (mavg = − 2.37) suggesting the protective role of PrPc in circulating RBC. The difference in the slope diminished during the 15 to 29 day period which was accompanied by a 50% decrease of PrPc surface expression on transfused WT RBC. To confirm our data the identical experiment was carried out in a group of KO mice (n=5) transfused with a mixture containing KO RBC labeled with low and WT RBC with high level of biotin. Again the first day post-transfusion recovery was higher for KO RBC (80 ± 6 % vs. 75 ± 6 %, P&lt;0.05) and the initial slope of the KO RBC survival curve was steeper in all mice in the group. Our data suggest that PrPc expression plays role in the post-transfusion recovery and survival of RBC. The observation that WT RBC disappear from the circulation at lower rate than KO RBC until their level of surface PrPc reaches 50% is compatible with the protective role of PrPc expression on cells. Taken together our study demonstrates that physiological role of PrPc expression on RBC may lay in facilitating their longer survival in circulation. (GACR 310/04/0419, MSMT 0021620806).

scholarly journals Neurotropic influenza A virus infection causes prion protein misfolding into infectious prions in neuroblastoma cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hideyuki Hara ◽  
Junji Chida ◽  
Keiji Uchiyama ◽  
Agriani Dini Pasiana ◽  
Etsuhisa Takahashi ◽  
...  
Keyword(s):  
Prion Protein ◽  
Influenza A Virus ◽  
Protein Misfolding ◽  
Influenza A ◽  
Prion Diseases ◽  
Neuroblastoma Cells ◽  
Cellular Prion Protein ◽  
Infected Cells ◽  
Hit And Run

AbstractMisfolding of the cellular prion protein, PrPC, into the amyloidogenic isoform, PrPSc, which forms infectious protein aggregates, the so-called prions, is a key pathogenic event in prion diseases. No pathogens other than prions have been identified to induce misfolding of PrPC into PrPSc and propagate infectious prions in infected cells. Here, we found that infection with a neurotropic influenza A virus strain (IAV/WSN) caused misfolding of PrPC into PrPSc and generated infectious prions in mouse neuroblastoma cells through a hit-and-run mechanism. The structural and biochemical characteristics of IAV/WSN-induced PrPSc were different from those of RML and 22L laboratory prions-evoked PrPSc, and the pathogenicity of IAV/WSN-induced prions were also different from that of RML and 22L prions, suggesting IAV/WSN-specific formation of PrPSc and infectious prions. Our current results may open a new avenue for the role of viral infection in misfolding of PrPC into PrPSc and formation of infectious prions.

scholarly journals The role of prion protein in stem cell regulation

Reproduction ◽  
2013 ◽  
Vol 146 (3) ◽  
pp. R91-R99 ◽  
Author(s):  
A Miranda ◽  
P Ramos-Ibeas ◽  
E Pericuesta ◽  
M A Ramirez ◽  
A Gutierrez-Adan
Keyword(s):  
Stem Cells ◽  
Prion Protein ◽  
Prion Diseases ◽  
Cellular Prion Protein ◽  
Important Advance ◽  
Self Renewal ◽  
Stem Cell Regulation ◽  
Pluripotency Gene ◽  
New Strategies

Cellular prion protein (PrPC) has been well described as an essential partner of prion diseases due to the existence of a pathological conformation (PrPSc). Recently, it has also been demonstrated that PrPCis an important element of the pluripotency and self-renewal matrix, with an increasing amount of evidence pointing in this direction. Here, we review the data that demonstrate its role in the transcriptional regulation of pluripotency, in the differentiation of stem cells into different lineages (e.g. muscle and neurons), in embryonic development, and its involvement in reproductive cells. Also highlighted are recent results from our laboratory that describe an important regulation by PrPCof the major pluripotency geneNanog. Together, these data support the appearance of new strategies to control stemness, which could represent an important advance in the field of regenerative medicine.

Expression of Cellular Prion Protein (PrPc) on Human Red Blood Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1898-1898 ◽  
Author(s):  
Martin Panigaj ◽  
Adela Brouckova ◽  
Hana Glierova ◽  
Karel Holada
Keyword(s):  
Red Blood Cells ◽  
Prion Protein ◽  
Blood Cells ◽  
Prion Diseases ◽  
Cellular Prion Protein ◽  
Proteinase K ◽  
Screening Tests ◽  
Specific Marker ◽  
Advanced Glycosylation End Products ◽  
Human Red Blood Cells

Abstract Two recent UK cases of vCJD transmission by blood transfusion emphasize urgent need of donor screening test for prion diseases. Pathological form of prion protein, PrPsc, is currently the only specific marker of prion diseases, but its detection in blood poses significant challenge. Blood contains substantial amount of normal PrPc which supposedly differs from PrPsc only in its conformation. Majority of cell associated PrPc in blood reside in platelets (PLT). PrPc is also expressed on PBMCs, but their contribution to quantity of blood PrPc is small. The situation is less clear with PrPc on red blood cells (RBC). Others and we have previously shown that PrPc is detectable on RBC by flow cytometry (FACS). However, this was contradicted by another study and by reported minimal content of PrPc in RBC measured by ELISA. To confirm our finding, we used quantitative FACS with fluorescein labeled monoclonal antibodies (MAbs) FH11, 3F4 and 6H4 against different parts of PrPc molecule (PrP23–85, PrP109–112 and PrP144–152, respectively) for evaluation of PrPc expression on RBC of healthy blood donors (n=8). Mean (range) of MAb molecules bound /cell was: FH11 - 36 (13–74), 3F4 - 80 (33–137), 6H4 - 258 (113–557). Interestingly, 3F4 and 6H4 recognized PrPc on PLT in the same samples equally well. Decrease accessibility of 3F4 epitope is one of the characteristics of PrPsc, suggesting that PrPc on RBC may adopt PrPsc like conformation. To test if PrPc on RBC is resistant to proteolysis we treated blood samples with increasing concentrations of proteinase K (1-50 mg/ml, 30 min., 0°C). FACS demonstrated gradual and complete cleavage of PrPc on both PLT and RBC. Lower 3F4 binding to RBC could be explained by expression of N-terminally truncated form of PrPc. Western blot (WB) analysis of RBC ghosts with MAbs 6H4 and AG4 (PrP31–51) confirmed the presence of PrPc in RBC membranes. PrPc seems to be mainly in diglycosylated form, detected as a diffuse band with molecular weight (m.w.) slightly higher (35–38 kDa) than brain PrPc. The difference in PrPc mobility diminished after deglycosylation of PrPc with PNGase. No prominent bands with lower m.w. suggesting presence of truncated PrPc in RBC were detected. If conformation was the cause of 3F4 epitope inaccessibility, this should be reversed by denaturation. Interestingly, 3F4 displayed similar deficiency in PrPc detection also on WB after denaturation of RBC samples with SDS and boiling. At the same time 3F4 and 6H4 exhibited similar sensitivity in detection of PrPc on WB of dilutions of brain or PLT lysate. The remaining explanation of 3F4 reactivity is that its epitope MKHM on RBC PrPc is modified. Recently, modification of Lys residues of PrPsc by advanced glycosylation end products (AGEs) has been reported. We modified Lys residues of brain PrPc on blots by treatment with increasing concentrations of paraformaldehyde and confirmed that Lys modification leads to loss of 3F4 binding. In opposite to situation in peripheral blood, PrPc on erythroid CD71+ cells in cord blood was detected equally well with 3F4 and 6H4, suggesting that modification of PrPc occurs after release of RBC into periphery. Taken together, human RBC express ~ 200 molecules of PrPc/cell. Due to high RBC count even such low level of expression suggests significant contribution to pool of cell associated PrPc in blood (~ 50%). Methods utilizing MAbs FH11 and 3F4 may underestimate quantity of PrPc in RBC. Likewise, screening tests for presence of PrPsc in blood may encounter difficulties if modification similar to one reported here is present.

Deletion of the Prion Protein Does not Affect Erythropoiesis in a Mouse Model of Beta-Thalassemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3213-3213
Author(s):  
Monique Gelderman-Fuhrmann ◽  
John Farrell ◽  
Martin Panigaj ◽  
Karel Holada ◽  
Jaroslav Vostal
Keyword(s):  
Mouse Model ◽  
Prion Protein ◽  
Blood Cells ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Cellular Prion Protein ◽  
Lower Percentage ◽  
Erythroid Precursor ◽  
Acute Anemia ◽  
Prnp Genotype

Abstract Abstract 3213 The cellular prion protein (PrPc) is a highly conserved GPI-linked cell surface sialoglycoprotein which plays a key role in the pathogenesis of neurodegenerative prion diseases. Although PrPc is conserved across species, its normal function is not clearly understood. PrPc tissue distribution varies by cell type or by level of expression in different species. Circulating red blood cells (RBCs) in humans and mice have similar levels of PrPc and reports in the literature suggest that it has a role in survival of cells under stress conditions. We previously reported that an absence of PrPc in PrPc knock out (Prnp-/-) mice negatively influenced their response to acute anemia induced with phenylhydrazine (PHZ) (Zivny et al. 2008. Blood Cells, Molecules and Diseases. 40: 302–307). Prpn-/- mice displayed a reduction of erythroid cells and erythropoietin production suggesting the importance of PrPc expression for stress erythropoiesis. In order to further explore this observation, we mated chronically anemic β-thalassemic (th3/+) male mice (generously donated by Dr. M Sadelein, NY) with female Prnp-/- mice. Th3/+ mice have a defect in the β chain of hemoglobin and have lower hematocrits (HCT). Their offspring, heterozygous for PrPc (Prnp+/−), were genotyped and anemic th3/+ Prnp+/− males were mated with non-anemic (WT) Prnp+/− females to produce mice for the study. The PrPc genotype of two cohorts of offspring combined (n=127 total), Prnp+/+ (18%), Prpn+/− (56%) and Prnp-/- (26%), did not show significant deviation from a Mendelian distribution. Similarly, the proportion of Prnp-/- genotype among anemic th3/+ offspring (29.5%) was slightly higher than the proportion of Prnp+/+ genotype (18.1%), suggesting that PrPc deletion does not lead to higher in utero mortality of th3/+ mice. Evaluation of the microhematocrit at 12 weeks of age demonstrated decreased HCT levels of th3/+ mice (37.4±5.0% and 35.1±2.9%) in comparison to their WT siblings (51.6±2.5% and 49.1±3.5%). No significant differences were detected among different Prnp genotypes in both th3/+ and WT mice. In order to test if PrPc expression in these mice is important for the recovery from acute anemia, the th3/+ and the WT siblings of all PrPc genotypes (n=6 per group) were injected with PHZ (80 mg/kg). The following parameters were measured over a 7 day period using standard methods: HCT levels, plasma erythropoietin (EPO) levels, peripheral reticulocyte count, percentage of cells in the spleen expressing CD71, and the weight of animals and their spleens at the end of the study. On day 7 after induction of acute anemic stress, plasma EPO levels were higher in th3/+ animals compared to WT animals, 1125±48.4 pg/mL and 338±104.5 pg/mL respectively. The percent of erythroid precursor cells (CD71+) were lower in th3/+ (10.0±0.7%) than in WT (21.8±2.8%) splenocytes but the spleen sizes were larger in the th3/+ mice. Hematocrits were not different with statistical significance between th3/+ (28.8±0.6%) and WT (31.5±0.75%) animals on day 7, but circulating reticulocyte counts were higher in th3/+ (54.2±4.9% vs. 40.9±3.8%) animals. The PrPc genotype (Prnp+/+, Prnp+/− and Prnp-/-) did not affect the results in either the th3/+ or WT animals. Th3/+ animals were chronically anemic and had inefficient erythropoiesis which produced a lower percentage of CD71+ cells, in spite of higher levels of plasma EPO in response to similar levels of hypoxic stress as in the WT mice. However, the overall RBC production of th3/+ mice in response to acute hypoxia was maintained by a large spleen size. The prion protein deletion did not affect the percent of RBC precursors or the final RBC output. Thus, prion protein expression does not appear to influence RBC production in a chronically anemic mouse model. The findings and conclusions in this abstract have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. (GAUK86408, GACR 310/08/0878) Disclosures: No relevant conflicts of interest to declare.

scholarly journals Pharmacological inactivation of the prion protein by targeting a folding intermediate

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Giovanni Spagnolli ◽  
Tania Massignan ◽  
Andrea Astolfi ◽  
Silvia Biggi ◽  
Marta Rigoli ◽  
...  
Keyword(s):  
Prion Protein ◽  
Prion Diseases ◽  
Cellular Prion Protein ◽  
Surface Glycoprotein ◽  
Folding Intermediate ◽  
Biological Regulation ◽  
Cell Surface Glycoprotein ◽  
Folding Intermediates ◽  
Protein Levels ◽  
Small Molecule Ligands

AbstractRecent computational advancements in the simulation of biochemical processes allow investigating the mechanisms involved in protein regulation with realistic physics-based models, at an atomistic level of resolution. These techniques allowed us to design a drug discovery approach, named Pharmacological Protein Inactivation by Folding Intermediate Targeting (PPI-FIT), based on the rationale of negatively regulating protein levels by targeting folding intermediates. Here, PPI-FIT was tested for the first time on the cellular prion protein (PrP), a cell surface glycoprotein playing a key role in fatal and transmissible neurodegenerative pathologies known as prion diseases. We predicted the all-atom structure of an intermediate appearing along the folding pathway of PrP and identified four different small molecule ligands for this conformer, all capable of selectively lowering the load of the protein by promoting its degradation. Our data support the notion that the level of target proteins could be modulated by acting on their folding pathways, implying a previously unappreciated role for folding intermediates in the biological regulation of protein expression.

scholarly journals Generation of Novel Human Red Blood Cell-Bearing Humanized Mouse Models Based on C3-Deficient NOG Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Takuya Yamaguchi ◽  
Ikumi Katano ◽  
Iyo Otsuka ◽  
Ryoji Ito ◽  
Misa Mochizuki ◽  
...  
Keyword(s):  
Mouse Models ◽  
Complement C3 ◽  
Humanized Mouse ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Human Red Blood Cells ◽  
Mouse Macrophages ◽  
C3 Gene ◽  
Humanized Mouse Models

Despite recent advances in immunodeficient mouse models bearing human red blood cells (hRBCs), the elimination of circulating hRBCs by residual innate immune systems remains a significant challenge. In this study, we evaluated the role of mouse complement C3 in the elimination of circulating hRBCs by developing a novel NOG substrain harboring a truncated version of the murine C3 gene (NOG-C3ΔMG2-3). Genetic C3 deletion prolonged the survival of transfused hRBCs in the circulation. Chemical depletion and functional impairment of mouse macrophages, using clodronate liposomes (Clo-lip) or gadolinium chloride (GdCl3), respectively, further extended the survival of hRBCs in NOG-C3ΔMG2-3 mice. Low GdCl3 toxicity allowed the establishment of hRBC-bearing mice, in which hRBCs survived for more than 4 weeks with transfusion once a week. In addition, erythropoiesis of human hematopoietic stem cells (hHSCs) was possible in NOG-C3ΔMG2-3/human GM-CSF-IL-3 transgenic mice with Clo-lip treatment. These findings indicate that mouse models harboring hRBCs can be achieved using NOG-C3ΔMG2-3 mice, which could facilitate studies of human diseases associated with RBCs.

scholarly journals The Role of Cellular Prion Protein in Cancer Biology: A Potential Therapeutic Target

2021 ◽  
Vol 11 ◽  
Author(s):  
Manqiu Ding ◽  
Yongqiang Chen ◽  
Yue Lang ◽  
Li Cui
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Cell Survival ◽  
Cancer Cells ◽  
Prion Protein ◽  
Therapeutic Target ◽  
Cancer Biology ◽  
Cellular Prion Protein ◽  
Potential Therapeutic Target

Prion protein has two isoforms including cellular prion protein (PrPC) and scrapie prion protein (PrPSc). PrPSc is the pathological aggregated form of prion protein and it plays an important role in neurodegenerative diseases. PrPC is a glycosylphosphatidylinositol (GPI)-anchored protein that can attach to a membrane. Its expression begins at embryogenesis and reaches the highest level in adulthood. PrPC is expressed in the neurons of the nervous system as well as other peripheral organs. Studies in recent years have disclosed the involvement of PrPC in various aspects of cancer biology. In this review, we provide an overview of the current understanding of the roles of PrPC in proliferation, cell survival, invasion/metastasis, and stem cells of cancer cells, as well as its role as a potential therapeutic target.

scholarly journals Prion protein and prion disease at a glance

2021 ◽  
Vol 134 (17) ◽  
Author(s):  
Caihong Zhu ◽  
Adriano Aguzzi
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Neurodegenerative Disorders ◽  
Prion Diseases ◽  
Amyloid Β ◽  
Cellular Prion Protein ◽  
Future Studies ◽  
Associated Proteins ◽  
Main Component ◽  
Conformational Conversion

ABSTRACT Prion diseases are neurodegenerative disorders caused by conformational conversion of the cellular prion protein (PrPC) into scrapie prion protein (PrPSc). As the main component of prion, PrPSc acts as an infectious template that recruits and converts normal cellular PrPC into its pathogenic, misfolded isoform. Intriguingly, the phenomenon of prionoid, or prion-like, spread has also been observed in many other disease-associated proteins, such as amyloid β (Aβ), tau and α-synuclein. This Cell Science at a Glance and the accompanying poster highlight recently described physiological roles of prion protein and the advanced understanding of pathogenesis of prion disease they have afforded. Importantly, prion protein may also be involved in the pathogenesis of other neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Therapeutic studies of prion disease have also exploited novel strategies to combat these devastating diseases. Future studies on prion protein and prion disease will deepen our understanding of the pathogenesis of a broad spectrum of neurodegenerative conditions.

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