Pub Date : 2018-11-05DOI: 10.5772/INTECHOPEN.80701
A. Ragagnin, Qili Wang, A. Guillemain, Siaka Dole, Anne-Sophie Wilding, V. Demais, C. Royer, A. Haeberlé, N. Vitale, S. Gasman, N. Grant, Y. Bailly
The cellular prion protein, a major player in the neuropathology of prion diseases, is believed to control both death and survival pathways in central neurons. However, the cellular and molecular mechanisms underlying these functions remain to be deciphered. This chapter presents cytopathological studies of the neurotoxic effects of infectious prions and cellular prion protein-deficiency on cerebellar neurons in wild-type and transgenic mice. The immunochemical and electron microscopy data collected in situ and ex vivo in cultured organotypic cerebellar slices indicate that an interplay between apoptotic and autophagic pathways is involved in neuronal death induced either by the infectious prions or by prion protein-deficiency.
{"title":"Prion Proteins and Neuronal Death in the Cerebellum","authors":"A. Ragagnin, Qili Wang, A. Guillemain, Siaka Dole, Anne-Sophie Wilding, V. Demais, C. Royer, A. Haeberlé, N. Vitale, S. Gasman, N. Grant, Y. Bailly","doi":"10.5772/INTECHOPEN.80701","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.80701","url":null,"abstract":"The cellular prion protein, a major player in the neuropathology of prion diseases, is believed to control both death and survival pathways in central neurons. However, the cellular and molecular mechanisms underlying these functions remain to be deciphered. This chapter presents cytopathological studies of the neurotoxic effects of infectious prions and cellular prion protein-deficiency on cerebellar neurons in wild-type and transgenic mice. The immunochemical and electron microscopy data collected in situ and ex vivo in cultured organotypic cerebellar slices indicate that an interplay between apoptotic and autophagic pathways is involved in neuronal death induced either by the infectious prions or by prion protein-deficiency.","PeriodicalId":433646,"journal":{"name":"Prions - Some Physiological and Pathophysiological Aspects","volume":"89 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123138948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-11-05DOI: 10.5772/INTECHOPEN.80702
Saima Zafar, N. Younas, M. Shafiq, I. Zerr
The infectious agents, prions, are composed mainly of conformational isomers of the cellular prion protein (PrPc) in its abnormal accumulated scrapie forms (PrPSc). The distinct prion isolates or strains have been associated with different PrPSc prion protein conformations and patterns of glycosylation and are associated with disease progression and severity. In humans, sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form and has been divided into six subtypes, based on PrPSc electrophoretic mobility and allelic variation at codon 129, among which sCJD MM1 and sCJD VV2 are the two most commonly occurring subtypes with known clinical manifestations. The strain-specific response of PrPSc suggests both the molecular classification and the pathogenesis of prion diseases along with posttranslational modification of PrP in humans and animals.
{"title":"Prion Protein Strain Diversity and Disease Pathology","authors":"Saima Zafar, N. Younas, M. Shafiq, I. Zerr","doi":"10.5772/INTECHOPEN.80702","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.80702","url":null,"abstract":"The infectious agents, prions, are composed mainly of conformational isomers of the cellular prion protein (PrPc) in its abnormal accumulated scrapie forms (PrPSc). The distinct prion isolates or strains have been associated with different PrPSc prion protein conformations and patterns of glycosylation and are associated with disease progression and severity. In humans, sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form and has been divided into six subtypes, based on PrPSc electrophoretic mobility and allelic variation at codon 129, among which sCJD MM1 and sCJD VV2 are the two most commonly occurring subtypes with known clinical manifestations. The strain-specific response of PrPSc suggests both the molecular classification and the pathogenesis of prion diseases along with posttranslational modification of PrP in humans and animals.","PeriodicalId":433646,"journal":{"name":"Prions - Some Physiological and Pathophysiological Aspects","volume":"49 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126269891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-11-05DOI: 10.5772/INTECHOPEN.78951
K. Uchiyama, S. Sakaguchi
A fundamental event in the pathogenesis of prion disease is the conversion of cellular prion protein into an abnormally folded isoform (PrP Sc ), which is the infectious causative agent of disease. With progression of disease, PrP Sc is replicated and excessively accumulated in most cases. However, the molecular mechanism for excessive accumulation of PrP Sc is not well understood. Recently, Sortilin, a member of the VPS10P domain receptor family, has been identified as a sorting receptor that directs prion protein (PrP) to the lysosomal degradation pathway. Moreover, it has been shown that prion infection impairs Sortilin function, resulting in delayed PrP Sc degradation. In this chapter, we explain the mechanisms for PrP trafficking into the lysosomal degradation pathway mediated by Sortilin and overaccumulation of PrP Sc caused by Sortilin dysfunction.
{"title":"A Molecular Mechanism for Abnormal Prion Protein Accumulation","authors":"K. Uchiyama, S. Sakaguchi","doi":"10.5772/INTECHOPEN.78951","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.78951","url":null,"abstract":"A fundamental event in the pathogenesis of prion disease is the conversion of cellular prion protein into an abnormally folded isoform (PrP Sc ), which is the infectious causative agent of disease. With progression of disease, PrP Sc is replicated and excessively accumulated in most cases. However, the molecular mechanism for excessive accumulation of PrP Sc is not well understood. Recently, Sortilin, a member of the VPS10P domain receptor family, has been identified as a sorting receptor that directs prion protein (PrP) to the lysosomal degradation pathway. Moreover, it has been shown that prion infection impairs Sortilin function, resulting in delayed PrP Sc degradation. In this chapter, we explain the mechanisms for PrP trafficking into the lysosomal degradation pathway mediated by Sortilin and overaccumulation of PrP Sc caused by Sortilin dysfunction.","PeriodicalId":433646,"journal":{"name":"Prions - Some Physiological and Pathophysiological Aspects","volume":"291 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"120879003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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