Next Article in Journal
MG132 Induces Progerin Clearance and Improves Disease Phenotypes in HGPS-like Patients’ Cells
Next Article in Special Issue
Species-Specific Gamete Interaction during Sea Urchin Fertilization: Roles of the Egg Jelly and Vitelline Layer
Previous Article in Journal
Activation of Immune System May Cause Pathophysiological Changes in the Myocardium of SARS-CoV-2 Infected Monkey Model
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Cells
Volume 11
Issue 4
10.3390/cells11040609
cells-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Calcineurin Controls Cellular Prion Protein Expression in Mouse Astrocytes

by
Giulia Dematteis
1,
Elena Restelli
2,
Virginia Vita Vanella
3,
Marcello Manfredi
3,
Emilio Marengo
4,
Marco Corazzari
5,
Armando A. Genazzani
1,
Roberto Chiesa
2,
Dmitry Lim
1,* and
Laura Tapella
1,*
1
Department of Pharmaceutical Sciences, Università del Piemonte Orientale “Amedeo Avogadro”, 28100 Novara, Italy
2
Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy
3
Department of Translational Medicine, Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale “Amedeo Avogadro”, 28100 Novara, Italy
4
Department of Sciences and Technological Innovation, Università del Piemonte Orientale “Amedeo Avogadro”, 28100 Novara, Italy
5
Department of Health Science (DSS), Center for Translational Research on Autoimmune and Allergic Disease (CAAD) & Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale “Amedeo Avogadro”, 28100 Novara, Italy
*
Authors to whom correspondence should be addressed.
Cells 2022, 11(4), 609; https://doi.org/10.3390/cells11040609
Submission received: 22 January 2022 / Revised: 4 February 2022 / Accepted: 8 February 2022 / Published: 10 February 2022
(This article belongs to the Special Issue Cell Calcium across the Phylogenetic Tree: From Physiological Signaling to Pathogenic Mechanisms)
Browse Figures
Versions Notes

Abstract

Prion diseases arise from the conformational conversion of the cellular prion protein (PrPC) into a self-replicating prion isoform (PrPSc). Although this process has been studied mostly in neurons, a growing body of evidence suggests that astrocytes express PrPC and are able to replicate and accumulate PrPSc. Currently, prion diseases remain incurable, while downregulation of PrPC represents the most promising therapy due to the reduction of the substrate for prion conversion. Here we show that the astrocyte-specific genetic ablation or pharmacological inhibition of the calcium-activated phosphatase calcineurin (CaN) reduces PrPC expression in astrocytes. Immunocytochemical analysis of cultured CaN-KO astrocytes and isolation of synaptosomal compartments from the hippocampi of astrocyte-specific CaN-KO (ACN-KO) mice suggest that PrPC is downregulated both in vitro and in vivo. The downregulation occurs without affecting the glycosylation of PrPC and without alteration of its proteasomal or lysosomal degradation. Direct assessment of the protein synthesis rate and shotgun mass spectrometry proteomics analysis suggest that the reduction of PrPC is related to the impairment of global protein synthesis in CaN-KO astrocytes. When WT-PrP and PrP-D177N, a mouse homologue of a human mutation associated with the inherited prion disease fatal familial insomnia, were expressed in astrocytes, CaN-KO astrocytes showed an aberrant localization of both WT-PrP and PrP-D177N variants with predominant localization to the Golgi apparatus, suggesting that ablation of CaN affects both WT and mutant PrP proteins. These results provide new mechanistic details in relation to the regulation of PrP expression in astrocytes, suggesting the therapeutic potential of astroglial cells.
Keywords: astrocytes; calcineurin; FK506; prion protein; protein synthesis; calcium; neuroinflammation astrocytes; calcineurin; FK506; prion protein; protein synthesis; calcium; neuroinflammation

Share and Cite

MDPI and ACS Style

Dematteis, G.; Restelli, E.; Vanella, V.V.; Manfredi, M.; Marengo, E.; Corazzari, M.; Genazzani, A.A.; Chiesa, R.; Lim, D.; Tapella, L. Calcineurin Controls Cellular Prion Protein Expression in Mouse Astrocytes. Cells 2022, 11, 609. https://doi.org/10.3390/cells11040609

AMA Style

Dematteis G, Restelli E, Vanella VV, Manfredi M, Marengo E, Corazzari M, Genazzani AA, Chiesa R, Lim D, Tapella L. Calcineurin Controls Cellular Prion Protein Expression in Mouse Astrocytes. Cells. 2022; 11(4):609. https://doi.org/10.3390/cells11040609

Chicago/Turabian Style

Dematteis, Giulia, Elena Restelli, Virginia Vita Vanella, Marcello Manfredi, Emilio Marengo, Marco Corazzari, Armando A. Genazzani, Roberto Chiesa, Dmitry Lim, and Laura Tapella. 2022. "Calcineurin Controls Cellular Prion Protein Expression in Mouse Astrocytes" Cells 11, no. 4: 609. https://doi.org/10.3390/cells11040609

APA Style

Dematteis, G., Restelli, E., Vanella, V. V., Manfredi, M., Marengo, E., Corazzari, M., Genazzani, A. A., Chiesa, R., Lim, D., & Tapella, L. (2022). Calcineurin Controls Cellular Prion Protein Expression in Mouse Astrocytes. Cells, 11(4), 609. https://doi.org/10.3390/cells11040609

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop