Serpin Signatures in Prion and Alzheimer's Diseases
| Autor: | Marco Zattoni, Marika Mearelli, Silvia Vanni, Arianna Colini Baldeschi, Thanh Hoa Tran, Chiara Ferracin, Marcella Catania, Fabio Moda, Giuseppe Di Fede, Giorgio Giaccone, Fabrizio Tagliavini, Gianluigi Zanusso, James W. Ironside, Isidre Ferrer, Giuseppe Legname |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Prion diseases
Prions Neuroscience (miscellaneous) metabolism [Neurodegenerative Diseases] Creutzfeldt-Jakob Syndrome Prion Diseases Cellular and Molecular Neuroscience pathology [Alzheimer Disease] Mice Alzheimer Disease ddc:570 Animals Humans Serpins pathology [Creutzfeldt-Jakob Syndrome] Brain Neurodegenerative Diseases Neurology metabolism [Brain] metabolism [Prions] SERPINA3/SerpinA3n Gene expression metabolism [Prion Diseases] Alzheimer’s disease Acute-Phase Proteins |
| Zdroj: | Molecular neurobiology 59, 3778-3799 (2022). doi:10.1007/s12035-022-02817-3 Zattoni, M, Mearelli, M, Vanni, S, Colini Baldeschi, A, Tran, T H, Ferracin, C, Catania, M, Moda, F, Di Fede, G, Giaccone, G, Tagliavini, F, Zanusso, G, Ironside, J W, Ferrer, I & Legname, G 2022, ' Serpin Signatures in Prion and Alzheimer’s Diseases ', Molecular Neurobiology . https://doi.org/10.1007/s12035-022-02817-3 |
| DOI: | 10.1007/s12035-022-02817-3 |
| Popis: | Serpins represent the most broadly distributed superfamily of proteases inhibitors. They contribute to a variety of physiological functions and any alteration of the serpin-protease equilibrium can lead to severe consequences. SERPINA3 dysregulation has been associated with Alzheimer’s disease (AD) and prion diseases. In this study, we investigated the differential expression of serpin superfamily members in neurodegenerative diseases. SERPIN expression was analyzed in human frontal cortex samples from cases of sporadic Creutzfeldt-Jakob disease (sCJD), patients at early stages of AD–related pathology, and age-matched controls not affected by neurodegenerative disorders. In addition, we studied whether Serpin expression was dysregulated in two animal models of prion disease and AD.Our analysis revealed that, besides the already observed upregulation of SERPINA3 in patients with prion disease and AD, SERPINB1, SERPINB6, SERPING1, SERPINH1, and SERPINI1 were dysregulated in sCJD individuals compared to controls, while only SERPINB1 was upregulated in AD patients. Furthermore, we analyzed whether other serpin members were differentially expressed in prion-infected mice compared to controls and, together with SerpinA3n, SerpinF2 increased levels were observed. Interestingly, SerpinA3n transcript and protein were upregulated in a mouse model of AD. The SERPINA3/SerpinA3nincreased anti-protease activity found in post-mortem brain tissue of AD and prion disease samples suggest its involvement in the neurodegenerative processes. A SERPINA3/SerpinA3n role in neurodegenerative disease-related protein aggregation was further corroborated by in vitro SerpinA3n-dependent prion accumulation changes. Our results indicate SERPINA3/SerpinA3n is a potential therapeutic target for the treatment of prion and prion-like neurodegenerative diseases. |
| Databáze: | OpenAIRE |
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