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ANALYSES OF THE DEVELOPMENT AND FUNCTION OF STEM CELL DERIVED CELLS IN NEURODEGENERATIVE DISEASES.pdfSailee Sham Lavekar (14152875) 03 February 2023 (has links)
<p>Human pluripotent stem cells (hPSCs) are an attractive tool for the study of different neurodegenerative diseases due to their potential to form any cell type of the body. Due to their versatility and self-renewal capacity, they have different applications such as disease modeling, high throughput drug screening and transplantation. Different animal models have helped answer broader questions related to the physiological functioning of various pathways and the phenotypic effects of a particular neurodegenerative disease. However, due to the lack of success recapitulating some targets identified from animal models into successful clinical trials, there is a need for a direct translational disease model. Since their advent, hPSCs have helped understand various disease effectors and underlying mechanisms using genetic engineering techniques, omics studies and reductionist approaches for the recognition of candidate molecules or pathways required to answer questions related to neurodevelopment, neurodegeneration and neuroregeneration. Due to the simplified approach that iPSC models can provide, some <em>in vitro</em> approaches are being developed using microphysiological systems (MPS) that could answer complex physiological questions. MPS encompass all the different <em>in vitro</em> systems that could help better mimic certain physiological systems that tend to not be mimicked by <em>in vivo</em> models. In this dissertation, efforts have been directed to disease model as well as to understand the intrinsic as well as extrinsic cues using two different MPS. First, we have used hPSCs with Alzheimer’s disease (AD)-related mutations to differentiate into retinal organoids and identify AD related phenotypes for future studies to identify retinal AD biomarkers. Using 5 month old retinal organoids from AD cell lines as well as controls, we could identify retinal AD phenotypes such as an increase in Aβ42:Aβ40 ratio along with increase in pTau:Tau. Nanostring analyses also helped in identification of potential target genes that are modulated in retinal AD that were related to synaptic dysfunction. Thus, using retinal organoids for the identification of retinal AD phenotypes could help delve deeper into the identification of future potential biomarkers in the retina of AD patients, with the potential to serve as a means for early identification and intervention for patients. The next MPS we used to serve to explore non-cell autonomous effects associated with glaucoma to explore the neurovascular unit. Previous studies have demonstrated the degeneration of RGCs in glaucoma due to a point mutation OPTN(E50K) that leads to the degeneration of RGCs both at morphological and functional levels. Thus, using the previous studies as a basis, we wanted to further unravel the impact of this mutation using the different cell types of the neurovascular unit such as endothelial cells, astrocytes and RGCs. Interestingly, we observed the barrier properties being impacted by the mutation present in both RGCs and astrocytes demonstrated through TEER, permeability and transcellular transport changes. We also identified a potential factor TGFβ2 that was observed to be overproduced by the OPTN E50K astrocytes to demonstrate similar effects with the exogenous addition of TGFβ2 on the barrier. Furthermore, the inhibition of TGFβ2 helped rescue some of the barrier dysfunction phenotypes. Thus, TGFβ2 inhibition can be used as a potential candidate that can be used to further study its impact in <em>in vivo</em> models and how that can be used in translational applications. Thus, MPS systems have a lot of applications that can help answer different physiologically relevant questions that are hard to approach using <em>in vivo</em> models and the further development of these systems to accentuate the aspects of neural development and how it goes awry in different neurodegenerative diseases. </p>
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P2X7 Receptors Amplify CNS Damage in Neurodegenerative DiseasesIlles, Peter 05 February 2024 (has links)
ATP is a (co)transmitter and signaling molecule in the CNS. It acts at a multitude of
ligand-gated cationic channels termed P2X to induce rapid depolarization of the cell membrane.
Within this receptor-channel family, the P2X7 receptor (R) allows the transmembrane fluxes of
Na+, Ca2+, and K+, but also allows the slow permeation of larger organic molecules. This is
supposed to cause necrosis by excessive Ca2+ influx, as well as depletion of intracellular ions
and metabolites. Cell death may also occur by apoptosis due to the activation of the caspase
enzymatic cascade. Because P2X7Rs are localized in the CNS preferentially on microglia, but also
at a lower density on neuroglia (astrocytes, oligodendrocytes) the stimulation of this receptor
leads to the release of neurodegeneration-inducing bioactive molecules such as pro-inflammatory
cytokines, chemokines, proteases, reactive oxygen and nitrogen molecules, and the excitotoxic
glutamate/ATP. Various neurodegenerative reactions of the brain/spinal cord following acute harmful
events (mechanical CNS damage, ischemia, status epilepticus) or chronic neurodegenerative diseases
(neuropathic pain, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral
sclerosis) lead to a massive release of ATP via the leaky plasma membrane of neural tissue.
This causes cellular damage superimposed on the original consequences of neurodegeneration. Hence,
blood-brain-barrier permeable pharmacological antagonists of P2X7Rs with excellent bioavailability
are possible therapeutic agents for these diseases. The aim of this review article is to summarize
our present state of knowledge on the involvement of P2X7R-mediated events in neurodegenerative
illnesses endangering especially the life quality and duration of the aged human population.
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Instability at Trinucleotide Repeat DNAsGadgil, Rujuta Yashodhan 30 August 2016 (has links)
No description available.
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Oral hälsa hos individer med Parkinson sjukdom : En allmän litteraturstudie / Oral health in individuals with Parkinson's diseaseIsaac, lulia, Shemoun, Mariam January 2022 (has links)
Syfte: Studiens syfte var att beskriva oral hälsa hos individer med Parkinson sjukdom (PS). Metod:Studiedesignen var i form av allmän litteraturstudie där tre databaser användes för sökning efter vetenskapliga artiklar (DOSS, CINAHL och MEDLINE). Efter tillämpning av inklusions-, exklusionskriterier, passande sökord samt genomförande av kvalitetsgranskning, valdes totalt 19 vetenskapliga artiklar. Resultat: Oral hygien tenderade till att vara sämre hos individer med PS. Resultatet visade att xerostomi och hyposalivation var vanligt förkommande hos individer med PS. Karies, gingivit och parodontit visades även hos individer med PS där bland annat parodontala mätningar visades vara högre till andel hos dessa individer. Andra orala tillstånd som visades bland individer med PS var dregling, dysfagi, halitosis och angulär cheilit. Slutsats: Hos individer med PS visades orala hälsan var sämre jämfört med individer utan PS. Risken att utsättas för orala sjukdomar exempelvis karies, gingivit och parodontit var högre hos individer med PS, där både läkemedelsintag och nedsatt motorik har en inverkan. / Aim: The aim was to describe oral health in individuals with Parkinson's disease (PD). Method: The study design was a general literature study where three databases were used to search for scientific articles (DOSS, CINAHL and MEDLINE). After applying inclusion, exclusion criteria, proper keywords and conducting a quality review, a total of 19 scientific articles were selected. Result: Oral hygiene tended to be worse in patients with PD. The results showed that xerostomia and hyposalivation are common in patients with PD. Caries, gingivitis and periodontitis were also shown among patients with PD where, among other things, periodontal measurements were shown to be higher in proportion in these individuals. Other oral conditions that were shown among individuals with PD were drooling, dysphagia, halitosis and angular cheilitis. Conclusion: Oral health was shown to be worse among individuals with PD compared to individuals without PD. The risk of being exposed to oral diseases such as caries, gingivitis and periodontitis was higher among these individuals where both drug intake and impaired motor skills have an effect.
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Génération de modèles cellulaires pour étudier l'impact du vieillissement sur la microglie humaineArmanville, Sandrine 08 1900 (has links)
Les microglies sont les cellules immunitaires du système nerveux central. Elles sont essentielles pour son bon fonctionnement et son homéostasie. Avec l’âge, elles adoptent une morphologie dystrophique accompagnée d’un dérèglement de leurs fonctions homéostatiques. Le dysfonctionnement microglial associé au vieillissement est soupçonné de contribuer à la progression de maladies neurodégénératives. Cependant, la cause de ces changements phénotypiques est peu connue, d’autant plus chez l’humain compte tenu du manque d’accessibilité des microglies humaines âgées vivantes pour le travail moléculaire in vitro. Les travaux présentés dans ce mémoire visent donc le développement d’un modèle cellulaire qui permettrait d’étudier l’impact du vieillissement cellulaire sur la microglie humaine. Dans ce mémoire, nous formulons l’hypothèse que l’induction chimique de la sénescence dans les microglies humaines induira rapidement des caractéristiques associées au vieillissement cellulaire alors que la reprogrammation microgliale directe à partir de cellules de peau d’individus âgés maintiendra la signature associée au vieillissement cellulaire de manière physiologique. Les résultats démontrent que les microglies dans lesquelles la sénescence est chimiquement induite présentent des caractéristiques phénotypiques de vieillissement cellulaire et un dérèglement de leurs fonctions homéostatiques. De plus, les produits cellulaires obtenus par la reprogrammation microgliale directe adoptent plusieurs caractéristiques clés de la microglie, mais certaines conditions de reprogrammation directe doivent encore être déterminées afin d’obtenir un produit cellulaire authentique. Ces techniques fourniront une source renouvelable de microglies humaines âgées pouvant être dérivée de patients, afin d’étudier l’impact du vieillissement sur leurs fonctions physiologiques et sur leur interaction avec les cellules du cerveau dans les maladies neurodégénératives. / Microglia are the resident immune cells of the central nervous system (CNS). They are essential for brain functioning and cerebral homeostasis. With age, they adopt a dystrophic morphology and a disruption of their homeostatic functions occurs. Microglial dysfunction associated with aging is believed to contribute to the progression of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. However, how aging confers to microglia this change in phenotype is still unknown, especially in human given the lack of accessibility of live human aged microglia for in vitro molecular work. As such, the work presented in this Master’s thesis aims the development of a cellular model in which the effect of aging on microglial function can be studied in human microglia. In this paper, we formulate the hypothesis that chemical induction of senescence in human microglia rapidly induces phenotypic characteristics of cellular aging, whereas direct microglial reprogramming from fibroblasts of elderly individuals will maintain the aging signature following cellular conversion. The results obtained show that microglia in which senescence is chemically induced show phenotypic characteristics of cellular aging as well as disruption of their homeostatic functions. On the other hand, cellular product obtained from microglial reprogramming adopt several key features of human microglia, but some direct microglial reprogramming conditions still need to be determined in order to obtain a cell product closely resembling human microglia. These two methods will provide a renewable source of patient-derived aged microglia to study the impact of aging on their physiological functions and on their interaction with other CNS cells in neurodegenerative diseases.
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Arteterapia en el envejecimiento y enfermedades neurodegenerativas. Experiencias basadas en la prevención, intervención y el activismo artístico.Marco Martínez, Patricia 15 July 2024 (has links)
Tesis por compendio / [ES] El aumento del envejecimiento de la población a nivel mundial y la limitada eficacia de los tratamientos disponibles para la demencia plantean la necesidad de desarrollar intervenciones dirigidas al envejecimiento y a las enfermedades neurodegenerativas. También se hace necesario promover cambios relacionados con la percepción negativa sobre la vejez en la sociedad. Ante estos planteamientos se está informando de los posibles beneficios terapéuticos de las intervenciones basadas en las artes, como la arteterapia, en la promoción de la salud, prevención de la demencia y manejo de la sintomatología asociada.
Debido al interés de este tema nos propusimos evaluar los principales efectos de la arteterapia en el envejecimiento y enfermedades neurodegenerativas, analizar los posibles beneficios de esta terapia dirigida a personas mayores durante la pandemia y conocer los efectos del arte respuesta como activismo artístico para promover el cambio social en los estereotipos asociados al envejecimiento.
Con el fin de alcanzar estos objetivos se plantearon 5 estudios que han dado lugar a los 5 artículos publicados en revistas de impacto que componen la tesis doctoral. El primer estudio incluye una revisión sistemática que analiza los beneficios de la arteterapia en personas con Enfermedad de Alzheimer (EA): los resultados informan de mejoras en bienestar, calidad de vida, estado anímico y depresión. El segundo artículo muestra un estudio de un caso de Parálisis Supranuclear Progresiva (un parkinsonismo atípico) evaluando posibles beneficios de la arteterapia en la sintomatología asociada a la enfermedad. Los resultados informan de mejoras significativas en expresión emocional, aspectos conductuales y relaciones sociales. El tercer trabajo analiza la relación entre EA y el duelo crónico basándose en un estudio de caso de EA, evaluando los efectos de la arteterapia en los síntomas cognitivos, somáticos y psicológicos. Se observó un impacto positivo en la expresión emocional, aspectos cognitivos (concentración, control, memoria), relaciones sociales y cambios en el sentido de identidad. El cuarto estudio describe una intervención de arteterapia en un grupo de mujeres de edad avanzada realizada durante las restricciones impuestas por la pandemia analizando las dificultades asociadas a este periodo y proponiendo su abordaje a través de la arteterapia. Los resultados sugieren mejoras en aspectos cognitivos (concentración, memoria y atención), expresión e identificación emocional, socialización y disminución de la ansiedad. El quinto estudio consta de dos proyectos relacionados (exposición virtual y talleres intergeneracionales) que tienen como denominador común el arte respuesta como activismo artístico, promoviendo la concienciación y el cambio social, y utilizando el arte respuesta para dar sentido y significado a las reflexiones relacionadas con el envejecimiento.
Las experiencias incluidas en las 5 publicaciones contribuyen a generar avance del conocimiento acerca de las posibles aplicaciones de la arteterapia en el envejecimiento, enfermedades neurodegenerativas y prevención de la demencia. También se muestra su utilidad para contrarrestar la privación sensorial y social que conllevan las situaciones de crisis como las vividas durante la pandemia. Además, se han diseñado intervenciones basadas en el activismo artístico que pueden contribuir a desafiar estereotipos y superar actitudes negativas de la sociedad hacia la vejez.
En futuros estudios sería de interés realizar intervenciones en muestras más amplias y con seguimiento longitudinal, así como el uso complementario de biomarcadores o técnicas de neuroimagen para evaluar los resultados de la intervención en la población de edad avanzada. Estas intervenciones arteterapéuticas pueden contribuir a crear experiencias participativas intergeneracionales basadas en las artes sobre la experiencia del envejecimiento / [CA] L'augment de l'envelliment de la població a nivell mundial i la limitada eficàcia dels tractaments disponibles per a la demència plantegen la necessitat de desenvolupar intervencions dirigides a l'envelliment i a les malalties neurodegeneratives. També es fa necessari promoure canvis relacionats amb la percepció negativa sobre la vellesa en la societat. Davant estos plantejaments s'està informant dels possibles beneficis terapèutics de les intervencions basades en les arts, com l'artteràpia, en la promoció de la salut, prevenció de la demència i maneig de la simptomatologia associada.
A causa de l'interés d'este tema ens vam proposar avaluar els principals efectes de l'artteràpia en l'envelliment i malalties neurodegeneratives, analitzar els possibles beneficis d'esta teràpia dirigida a persones majors durant la pandèmia i conéixer els efectes de l'art resposta com a activisme artístic per a promoure el canvi social en els estereotips associats a l'envelliment.
Amb la finalitat d'aconseguir estos objectius es van plantejar 5 estudis que han donat lloc als 5 articles publicats en revistes d'impacte que componen la tesi doctoral. El primer estudi inclou una revisió sistemàtica que analitza els beneficis de l'artteràpia en persones amb Malaltia d'Alzheimer: els resultats informen de millores en benestar, qualitat de vida, estat anímic i depressió. El segon article mostra un estudi de cas de Paràlisis Supranuclear Progressiva (un parkinsonisme atípic) avaluant possibles beneficis de l'artteràpia en la simptomatologia associada a la malaltia. Els resultats informen de millores significatives en expressió emocional, aspectes conductuals i relacions socials. El tercer treball analitza la relació entre Malaltia d'Alzheimer i el dol crònic basant-se en un estudi de un cas de Malaltia d'Alzheimer, avaluant els efectes de l'artteràpia en els símptomes cognitius, somàtics i psicològics. Es va observar un impacte positiu en l'expressió emocional, aspectes cognitius (concentració, control, memòria), relacions socials i canvis en el sentit d'identitat. El quart estudi descriu una intervenció d'artteràpia en un grup de dones d'edat avançada realitzada durant les restriccions imposades per la pandèmia analitzant les dificultats associades a este període i proposant el seu abordatge a través de l'artteràpia. Els resultats suggerixen millores en aspectes cognitius (concentració, memòria i atenció), expressió i identificació emocional, socialització i disminució de l'ansietat. El quint estudi consta de dos projectes relacionats (exposició virtual i tallers intergeneracionals) que tenen com a denominador comú l'art resposta com a activisme artístic, promovent la conscienciació i canvi social, i utilitzant l'art resposta per a donar sentit i significat a les reflexions relacionades amb l'envelliment.
Les experiències incloses en les 5 publicacions contribuïxen a generar avanç del coneixement sobre les possibles aplicacions de l'artteràpia en l'envelliment, malalties neurodegeneratives i prevenció de la demència. També es mostra la seua utilitat per a contrarestar la privació sensorial i social que comporten les situacions de crisis com les viscudes durant la pandèmia. A més, s'han dissenyat intervencions basades en l'activisme artístic que poden contribuir a desafiar estereotips i superar actituds negatives de la societat cap a la vellesa.
En futurs estudis seria d'interés realitzar intervencions en mostres més àmplies i amb seguiment longitudinal, així com l'ús complementari de biomarcadors o tècniques de neuroimatgeria per a avaluar els resultats de la intervenció en la població d'edat avançada. Estes intervencions artterapèutiques poden contribuir a crear experiències participatives intergeneracionals basades en les arts sobre l'experiència de l'envelliment / [EN] The increasing aging of the world's population and the limited effectiveness of available treatments for dementia increase the need to develop interventions that target aging and neurodegenerative diseases. There is also a need to promote changes in negative societal perceptions of old age. In light of these approaches, the potential therapeutic benefits of arts-based interventions, such as art therapy, in health promotion, dementia prevention and management of associated symptoms are being reported.
Due to the interest of this topic, we proposed to evaluate the main effects of art therapy in ageing and neurodegenerative diseases, to analyze the possible benefits of this therapy for older people during the pandemic, and to know the effects of response art as artistic activism to promote social change in the stereotypes associated with ageing.
In order to achieve these objectives, 5 studies were proposed, which gave rise to the 5 articles published in high impact journals that make up the thesis. The first study is a systematic review analyzing the benefits of art therapy in people with Alzheimer's disease: the results report improvements in well-being, quality of life, mood and depression. The second article presents a case study of a person living with Progressive Supranuclear Palsy (atypical parkinsonism), evaluating the potential benefits of art therapy on the symptomatology associated with the disease. The results report significant improvements in emotional expression, behavioral aspects and social relationships. The third paper analyses the relationship between Alzheimer's disease and chronic grief based on a case study of a woman diagnosed with Alzheimer's disease, evaluating the effects of art therapy on cognitive, somatic and psychological symptoms. Positive effects were observed on emotional expression, cognitive aspects (concentration, control, memory), social relationships and changes in sense of identity. The fourth study describes an art therapy intervention with a group of old women, carried out during the restrictions imposed by the pandemic, analyzing the difficulties associated with this period and proposing an approach through art therapy. The results suggest improvements in cognitive aspects (concentration, memory and attention), emotional expression and identification, socialization and reduction of anxiety. The fifth study consists of two related projects (virtual exhibition and intergenerational workshops) that share the common denominator of Response Art as artistic activism, promoting awareness and social change, and using Response Art to give sense and meaning to reflections related to aging.
The experiences included in the 5 publications contribute to the advancement of knowledge about the possible applications of art therapy in ageing, neurodegenerative diseases and dementia prevention. They also demonstrate its usefulness in counteracting the sensory and social deprivation associated with crisis situations such as those experienced during the pandemic. In addition, interventions based on artistic activism have been developed that can help to challenge stereotypes and overcome negative societal attitudes towards old age.
In future studies, it would be interesting to carry out interventions in larger samples and with longitudinal follow-up, as well as the complementary use of biomarkers or neuroimaging techniques to assess the results of the intervention with older people. These art-therapeutic interventions can contribute to the creation of art-based intergenerational participatory experiences of aging / Marco Martínez, P. (2024). Arteterapia en el envejecimiento y enfermedades neurodegenerativas. Experiencias basadas en la prevención, intervención y el activismo artístico [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/206125 / Compendio
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CRMP1 protein complexes modulate polyQ-mediated Htt aggregation and toxicity in neuronsBounab, Yacine 25 August 2010 (has links)
Chorea Huntington (HD) ist eine neurodegenerative Erkrankung, die durch Ablagerungen von N-terminal Polyglutamin-reichen Huntingtin (Htt) -Fragmenten in den betroffenen Neuronen charakterisiert ist. Das mutierte Htt (mHtt) Protein wird ubiquitär exprimiert. Das zellspezifische Absterben von „medium-sized spiny neurons“ (MSN) wird jedoch im Striatum von HD Patienten verursacht (Albin, 1995). Es wird angenommen, dass Striatum-spezifische Proteine, die mit Htt interagieren, eine wichtige Rolle in der Pathogenese von HD spielen (Ross, 1995). Protein-Protein-Interaktionsstudien haben gezeigt, dass einige der Htt-Interaktionspartner mit unlöslichen Htt-Ablagerungen in den Gehirnen von HD-Patienten kolokalisieren und die Bildung von Protein-Aggregaten beeinflussen (Goehler, 2004). Kürzlich wurde durch die Integration von Genexpressions- und Interaktionsdaten ein Striatum-spezifisches Protein-Interaktionsnetzwerk erstellt (Chaurasia, unveröffentlichte Daten). Eines der identifizierten Proteine ist CRMP1 (collapsin response mediator protein 1), das spezifisch in Neuronen exprimiert wird und möglicherweise eine wichtige Rolle bei der Pathogenese von HD spielt. Experimentelle Untersuchungen mithilfe eines Filter-Retardationsassays zeigten, dass CRMP1 die Anordnung von Htt zu fibrillären, SDS-unlöslichen Aggregaten verringert. Durch Rasterkraftmikroskopie wurde der direkte Effekt von CRMP1 auf den Aggregationsprozess von Htt bestätigt. Ko-Immunopräzipitationsstudien zeigten, dass CRMP1 und Htt in Säugerzellen unter physiologischen Bedingungen miteinander interagieren. Es wurde nachgewiesen, dass CRMP1 die Polyglutamin-abhängige Aggregation und Toxizität von Htt in Zell- und Drosophila-Modellen von HD moduliert. Außerdem konnte CRMP1 in neuronalen Ablagerungen in R6/2 Mäusegehirnen und dessen selektive Spaltung durch Calpaine gezeigt werden. Diese Ergebnisse deuten darauf hin, dass die Lokalisation und Funktion von CRMP1 bei der Krankheitsentstehung verändert werden. / Huntington’s disease (HD) is a neurodegenerative disorder characterized by the accumulation of N-terminal polyglutamine (polyQ)-containing huntingtin (Htt) fragments in affected neurons. The mutant Htt (mHtt) protein is ubiquitously expressed but causes specific dysfunction and death of striatal medium-sized spiny neurons (MSNs) (Albin, 1995). It is assumed that striatum specific proteins interacting with Htt might play an important role in HD pathogenesis (Ross, 1995). Previous protein-protein interaction (PPI) studies demonstrated that many Htt-interacting proteins colocalize with insoluble Htt inclusions in HD brains and modulate the mHtt phenotype (Goehler 2004). A striatum-specific, dysregulated PPI network has been created recently by integrating PPI networks with information from gene expression profiling data (Chaurasia, unpublished data). One of the identified dysregulated proteins potentially involved in HD pathogenesis was the neuron-specific collapsin response-mediator protein 1 (CRMP1). Here, I show that CRMP1 reduces the self-assembly of SDS-insoluble mHtt protein aggregates in vitro, indicating a direct role of CRMP1 on the mHtt aggregation process. Coimmunoprecipitation studies showed that CRMP1 and Htt associate in mammalian cells under physiological conditions. In addition, CRMP1 localizes to abnormal neuronal inclusions and efficiently modulates polyQ-mediated Htt aggregation and toxicity in cell and Drosophila models of HD. This suggests that dysfunction of the protein is crucial for disease pathogenesis. Finally, I observed that CRMP1 localizes to neuronal inclusions and is selectively cleaved by calpains in R6/2 mouse brains, indicating that its distribution and function are altered in pathogenesis. In conclusion, this study presents new findings on the function of CRMP1 and its role in the pathogenesis of HD. The protein interacts with Htt and modulates its aggregation and toxicity, in this way influencing the molecular course of the disease.
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Einfluss des Proteinaggregationshemmstoffs anle138b auf Beginn und Verlauf der Amyotrophen Lateralsklerose im transgenen hSOD1-Mausmodell / Influence of the protein aggregation inhibitor anle138b on the beginning and progression of amyotrophic lateral sclerosis in the transgenic hSOD1 mouse modelThyssen, Stella 24 June 2014 (has links)
No description available.
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Item Response Theory in the Neurodegenerative Disease Data Analysis / Théorie de la réponse d'item dans l'analyse des données sur les maladies neurodégénérativesWang, Wenjia 21 June 2017 (has links)
Les maladies neurodégénératives, telles que la maladie d'Alzheimer (AD) et Charcot Marie Tooth (CMT), sont des maladies complexes. Leurs mécanismes pathologiques ne sont toujours pas bien compris et les progrès dans la recherche et le développement de nouvelles thérapies potentielles modifiant la maladie sont lents. Les données catégorielles, comme les échelles de notation et les données sur les études d'association génomique (GWAS), sont largement utilisées dans les maladies neurodégénératives dans le diagnostic, la prédiction et le suivi de la progression. Il est important de comprendre et d'interpréter ces données correctement si nous voulons améliorer la recherche sur les maladies neurodégénératives. Le but de cette thèse est d'utiliser la théorie psychométrique moderne: théorie de la réponse d’item pour analyser ces données catégoriques afin de mieux comprendre les maladies neurodégénératives et de faciliter la recherche de médicaments correspondante. Tout d'abord, nous avons appliqué l'analyse de Rasch afin d'évaluer la validité du score de neuropathie Charcot-Marie-Tooth (CMTNS), un critère important d'évaluation principal pour les essais cliniques de la maladie de CMT. Nous avons ensuite adapté le modèle Rasch à l'analyse des associations génétiques pour identifier les gènes associés à la maladie d'Alzheimer. Cette méthode résume les génotypes catégoriques de plusieurs marqueurs génétiques tels que les polymorphisme nucléotidique (SNPs) en un seul score génétique. Enfin, nous avons calculé l'information mutuelle basée sur la théorie de réponse d’item pour sélectionner les items sensibles dans ADAS-cog, une mesure de fonctionnement cognitif la plus utilisées dans les études de la maladie d'Alzheimer, afin de mieux évaluer le progrès de la maladie. / Neurodegenerative diseases, such as Alzheimer’s disease (AD) and Charcot Marie Tooth (CMT), are complex diseases. Their pathological mechanisms are still not well understood, and the progress in the research and development of new potential disease-modifying therapies is slow. Categorical data like rating scales and Genome-Wide Association Studies (GWAS) data are widely utilized in the neurodegenerative diseases in the diagnosis, prediction and progression monitor. It is important to understand and interpret these data correctly if we want to improve the disease research. The purpose of this thesis is to use the modern psychometric Item Response Theory to analyze these categorical data for better understanding the neurodegenerative diseases and facilitating the corresponding drug research. First, we applied the Rasch analysis in order to assess the validity of the Charcot-Marie-Tooth Neuropathy Score (CMTNS), a main endpoint for the CMT disease clinical trials. We then adapted the Rasch model to the analysis of genetic associations and used to identify genes associated with Alzheimer’s disease by summarizing the categorical genotypes of several genetic markers such as Single Nucleotide Polymorphisms (SNPs) into one genetic score. Finally, to select sensitive items in the most used psychometrical tests for Alzheimer’s disease, we calculated the mutual information based on the item response model to evaluate the sensitivity of each item on the ADAS-cog scale.
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A critical analysis of the present neuropsychological and neuroanatomical theories and knowledge of art perception and artistic production taking creativity into accountRomp, Andreas Johannes 01 1900 (has links)
Text in English / The present paper analyses the neuroanatomical and neuropsychological backgrounds of art reception and art creation in modern visual art and creative processes. It critically presents two models of aesthetic experience to provide a comprehensive theoretical basis for the discussion. The research purpose is to show
that with increasing experience and expertise the referential frame of the aesthetic judgment is changing and that neural processes involved in object recognition provide a starting point for visual aesthetics. Thus, the investigation focuses on constructing and testing neuropsychological theories that fall in the domain called
'neuroaesthetics'. These theories, in turn, serve as a starting point to formulate neural laws of art and aesthetics and aesthetic experience. Some artistic styles, such as expressionism, reflect specific neural processes. Various studies indicate correlations between hemispheric specialisation and art or creativity and show the right hemisphere plays a particular role in it. However, studies exploring the neural
correlates of aesthetic preference have yielded mixed results. Furthermore, neuroimaging studies have proved that different categories of modern artworks are processed in different areas of the brain. These diverging results will be discussed in a critical assessment of the two models of aesthetic experience. Besides, the
question of identifying exclusive neural correlates of aesthetic preference will be raised.
Comparing amateurs and experts has revealed the more reduced the cortical
activation, the more efficiently it works.
Biological and neuropsychological factors of creativity point out the meaning of the activation level, cognitive inhibition and prefrontal cortex. Divergent thinking differs from convergent thinking in terms of the neural level.
Neurodegenerative processes and brain injuries sometimes influence the artistic output surprisingly or even launch it. Lesion studies contributing to understanding art experience will be explained. / Psychology / M.A. (Psychology)
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