Prion diseases are perhaps the most mysterious and peculiar diseases in nature. These diseases do not rely on the general dogmas of modern biology, seen in other infectious diseases caused by conventional pathogens, such as viruses and bacteria. On the contrary, their infectious agent is an unconventional proteinaceous pathogen, termed prion, that lacks functional nucleic acids. Prion diseases are also known as Transmissible Spongiform Encephalopathies (TSEs), since the diseases are transmissible from one host to another and manifest a spongiform appearance as result of the destruction of brain tissue during a long incubation period. Prion diseases include Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy (BSE, “mad cow disease”) in ruminants, scrapie in sheep and goats and chronic wasting disease in deer and elks. As demonstrated in the BSE outbreak and its transmission to humans, the onset of diseases is not limited to a certain species but can be transmissible from one host species to another. Such a striking nature of prions has generated huge concerns in public health and attracted serious attention in the scientific communities. To date, the potential transmission of prions to human has not been alleviated and TSEs still have no reliable preclinical screening tests and effective treatments. This doctoral thesis deals widely with the prion diseases, from epidemiology to pathogenesis, from diagnosis to therapy and prevention. Moreover it describes in detail three experimental projects aimed to clarify different aspects of TSEs. In all of them wild-type mouse bioassays are used, as they are the gold standard for assessing the biological properties of prions. The goal of the first study was to assess the therapeutic and/or preventive activity on TSEs of the chronic administration of a new γ-secretase modulator. The second research investigated the ability to identify BSE in presence of scrapie. The third project was aimed to study the effects induced by chronic administration of lipid enriched/depleted specific diets on the pathogenesis of prion diseases.

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES (TSES): EXPERIMENTAL APPROACHES TO PATHOGENESIS, THERAPY AND PREVENTION IN ANIMAL MODELS / E. Corda ; supervisore: P.E. Dall'Ara. Universita' degli Studi di Milano, 2012 Feb 03. 24. ciclo, Anno Accademico 2011. [10.13130/corda-erica_phd2012-02-03].

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES (TSES): EXPERIMENTAL APPROACHES TO PATHOGENESIS, THERAPY AND PREVENTION IN ANIMAL MODELS

E. Corda
2012

Abstract

Prion diseases are perhaps the most mysterious and peculiar diseases in nature. These diseases do not rely on the general dogmas of modern biology, seen in other infectious diseases caused by conventional pathogens, such as viruses and bacteria. On the contrary, their infectious agent is an unconventional proteinaceous pathogen, termed prion, that lacks functional nucleic acids. Prion diseases are also known as Transmissible Spongiform Encephalopathies (TSEs), since the diseases are transmissible from one host to another and manifest a spongiform appearance as result of the destruction of brain tissue during a long incubation period. Prion diseases include Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy (BSE, “mad cow disease”) in ruminants, scrapie in sheep and goats and chronic wasting disease in deer and elks. As demonstrated in the BSE outbreak and its transmission to humans, the onset of diseases is not limited to a certain species but can be transmissible from one host species to another. Such a striking nature of prions has generated huge concerns in public health and attracted serious attention in the scientific communities. To date, the potential transmission of prions to human has not been alleviated and TSEs still have no reliable preclinical screening tests and effective treatments. This doctoral thesis deals widely with the prion diseases, from epidemiology to pathogenesis, from diagnosis to therapy and prevention. Moreover it describes in detail three experimental projects aimed to clarify different aspects of TSEs. In all of them wild-type mouse bioassays are used, as they are the gold standard for assessing the biological properties of prions. The goal of the first study was to assess the therapeutic and/or preventive activity on TSEs of the chronic administration of a new γ-secretase modulator. The second research investigated the ability to identify BSE in presence of scrapie. The third project was aimed to study the effects induced by chronic administration of lipid enriched/depleted specific diets on the pathogenesis of prion diseases.
3-feb-2012
Settore VET/05 - Malattie Infettive degli Animali Domestici
prion ; transmissible spongiform encephalopathy ; TSEs ; scrapie ; bovine spongiform encephalopathy ; BSE ; lipid rafts ; Alzheimer's Disease ; coinfection ; γ-secretase modulator ; wild-type mice ; ruminant ; misfolding ; PrPSc
DALL'ARA, PAOLA EMANUELA
DALL'ARA, PAOLA EMANUELA
Doctoral Thesis
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES (TSES): EXPERIMENTAL APPROACHES TO PATHOGENESIS, THERAPY AND PREVENTION IN ANIMAL MODELS / E. Corda ; supervisore: P.E. Dall'Ara. Universita' degli Studi di Milano, 2012 Feb 03. 24. ciclo, Anno Accademico 2011. [10.13130/corda-erica_phd2012-02-03].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/169556
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