رسالة جامعية
Modelling Parkinson in zebrafish: from understanding disease to discovering new therapies
| العنوان: | Modelling Parkinson in zebrafish: from understanding disease to discovering new therapies |
|---|---|
| المؤلفون: | García Fernández, Jéssica |
| المساهمون: | University/Department: Universitat Pompeu Fabra. Departament de Medicina i Ciències de la Vida |
| مرشدي الرسالة: | Terriente, Javier, Santis, Flavia de |
| المصدر: | TDX (Tesis Doctorals en Xarxa) |
| بيانات النشر: | Universitat Pompeu Fabra, 2023. |
| سنة النشر: | 2023 |
| وصف مادي: | 266 p. |
| مصطلحات موضوعية: | Parkinson’s disease, zebrafish larvae, dopaminergic neurons, dysfunctional locomotion, CRISPR/Cas9, Sistema Inmune, disfunción mitocondrial, genes asociados a enfermedad de Párkinson, transcriptómica, patogénesis |
| الوقت: | 616.8 |
| الوصف: | The term "neurodegenerative disorder" refers to a set of illnesses in which the neurological system gradually deteriorates and is characterized by cognitive impairment, motor degradation, and behavioural changes. The second-most prevalent neurodegenerative condition among them is Parkinson's disease (PD). Environmental and genetic variables combine intricately to cause PD, according to the aetiology. The latter affects 10–20% of patients, and many genes have been identified as a contributing factor. As Parkinson's disease cannot currently be prevented, slowed, or cured, the identification of novel biomarkers is of utmost relevance for the development of successful pharmacological therapy. In order to shed light on the pathogenic underpinnings of this crippling disease, it is crucial to create animal models that mimic the onset, course, and symptomatology of the pathology. This thesis' major goal is to create a set of genetic and pharmacological zebrafish models of Parkinson's disease that may be used to find new therapeutic targets and medications that could be effective in treating the disease. The findings of this thesis project show that the selected genetic models - overexpression of park1/snca and loss-of-function of park2/parkin, park6/pink1, park7/DJ-1, and park8/lrrk2 - exhibit a subset of phenotypes that are consistent with those observed in Parkinson's disease patients, namely defects in locomotion and loss of dopaminergic neurons. Transcriptomic data from neurons isolated from the same genetic models reveal numerous dysregulated genes that have been previously linked to Parkinson's disease or to symptoms related to the disease, such as mitochondrial dysfunction, inflammatory response, or death. Overall, the work done for this thesis project has created a strong in vivo platform that can be used to find new therapeutic targets and, more significantly, to validate those targets and prospective compounds that could be used to modulate their activity. |
| الوصف (مترجم): | The term "neurodegenerative disorder" refers to a set of illnesses in which the neurological system gradually deteriorates and is characterized by cognitive impairment, motor degradation, and behavioural changes. The second-most prevalent neurodegenerative condition among them is Parkinson's disease (PD). Environmental and genetic variables combine intricately to cause PD, according to the aetiology. The latter affects 10–20% of patients, and many genes have been identified as a contributing factor. As Parkinson's disease cannot currently be prevented, slowed, or cured, the identification of novel biomarkers is of utmost relevance for the development of successful pharmacological therapy. In order to shed light on the pathogenic underpinnings of this crippling disease, it is crucial to create animal models that mimic the onset, course, and symptomatology of the pathology. This thesis' major goal is to create a set of genetic and pharmacological zebrafish models of Parkinson's disease that may be used to find new therapeutic targets and medications that could be effective in treating the disease. The findings of this thesis project show that the selected genetic models - overexpression of park1/snca and loss-of-function of park2/parkin, park6/pink1, park7/DJ-1, and park8/lrrk2 - exhibit a subset of phenotypes that are consistent with those observed in Parkinson's disease patients, namely defects in locomotion and loss of dopaminergic neurons. Transcriptomic data from neurons isolated from the same genetic models reveal numerous dysregulated genes that have been previously linked to Parkinson's disease or to symptoms related to the disease, such as mitochondrial dysfunction, inflammatory response, or death. Overall, the work done for this thesis project has created a strong in vivo platform that can be used to find new therapeutic targets and, more significantly, to validate those targets and prospective compounds that could be used to modulate their activity. Programa de Doctorat en Biomedicina |
| نوع الوثيقة: | Dissertation/Thesis |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | http://hdl.handle.net/10803/688560Test |
| حقوق: | ADVERTIMENT. Tots els drets reservats. L'accés als continguts d'aquesta tesi doctoral i la seva utilització ha de respectar els drets de la persona autora. Pot ser utilitzada per a consulta o estudi personal, així com en activitats o materials d'investigació i docència en els termes establerts a l'art. 32 del Text Refós de la Llei de Propietat Intel·lectual (RDL 1/1996). Per altres utilitzacions es requereix l'autorització prèvia i expressa de la persona autora. En qualsevol cas, en la utilització dels seus continguts caldrà indicar de forma clara el nom i cognoms de la persona autora i el títol de la tesi doctoral. No s'autoritza la seva reproducció o altres formes d'explotació efectuades amb finalitats de lucre ni la seva comunicació pública des d'un lloc aliè al servei TDX. Tampoc s'autoritza la presentació del seu contingut en una finestra o marc aliè a TDX (framing). Aquesta reserva de drets afecta tant als continguts de la tesi com als seus resums i índexs. |
| رقم الانضمام: | edstdx.10803.688560 |
| قاعدة البيانات: | TDX |
| الوصف غير متاح. |