Spelling suggestions: "subject:" alzheimer's disease""
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Diagnostika neurodegenerativních chorob pomocí Ramanovy spektroskopie / Diagnostics of neurodegenerative diseases by means of Raman spectroscopyKlener, Jakub January 2011 (has links)
Therapies of neurodegenerative diseases are often very difficult and their success depend on an early diagnose. From that reason we have been developing new diagnostic method for multiple sclerosis and Alzheimer disease by drop coating deposition Raman (DCDR) spectroscopy of cerebrospinal fluid (CSF) in this work. We found out conditions of measurements, where spectra were reproducible and accepted for standard diagnostic practices. We discovered that CSF has fast degradation at a room temperature, which was detectable in spectra after 5 hours, and degradation due to refreezing. DCDR spectra of CSF from individual patients were analyzed by factor and cluster analysis. Multiple sclerosis was manifested by lower intensity of a Raman band at 1080 cm−1 , which is probably connected with more general pathologic state. Spectral changes caused by Alzeheimer disease were more complex and beside changes mentioned above also changes connected with composition and conformation of proteins were identified in regions 1200-1800 cm−1 and 2870-2950 cm−1 . Additionally, we succeeded in distinguishing of young healthy patients from older patients in DCDR spectra. In this work were checked up, that DCDR is good diagnostic method for clinical practices for determining neurodegenerative diseases through the complex...
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Porovnání transgenního a streptozotocinového modelu Alzheimerovy choroby: validace systému IntelliCage pro behaviorální fenotypizaci / Comparison of transgenic and streptozotocin models of Alzheimer in rats: validation of IntelliCage system for behavioral phenotypizationSvobodová, Eva January 2021 (has links)
Animal models of Alzheimer's disease display cognitive insufficiencies which mimic human symptoms and occur at a given age or post-treatment time. Animals are typically tested using canonical behavioral tests, lasting minutes and taking place mostly in the non-active period of the daily cycle. Animals are exposed to certain amounts of manipulation-induced stress. Our work represents a validation study for the rat behavioral system IntelliCage. The tested individuals live freely in a group and their behavior is monitored continuously. It is however possible to set up individual tests for each animal or a group of animals. The rats are not subject to human manipulation and hence the results are not affected by manipulation-induced stress. We tested early cognitive impairment in the transgenic rat model TgF344-AD at 6 - 8 months of age. Further, we tested two most common protocols of the streptozotocin model, i.e. single dose of intracerebroventricular 3 mg/kg streptozotocin and double dose 48 hrs apart. Results were compared with the canonical Morris Water Maze (MWM) test. In the MWM test, transgenic animals did not differ from controls in any of the studied parameters. The streptozotocin model displayed a deficit only in the double dose group. However in the IntelliCage, transgenic animals displayed...
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Structure, Aggregation, and Inhibition of Alzheimer's B-Amyloid PeptideWang, Qiuming 28 August 2013 (has links)
No description available.
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Impaired Balance of Mitochondria Fission and Fusion in Alzheimer DiseaseWang, Xinglong January 2009 (has links)
No description available.
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Terahertz Spectroscopic Characterization and Imaging for Biomedical ApplicationsYeo, Woon Gi 14 August 2015 (has links)
No description available.
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Insights into the mechanism of Tau polymerization and the effects of small moleculesCongdon, Erin Elizabeth 06 August 2007 (has links)
No description available.
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[pt] PARA LEMBRAR-ME DE MIM: PRODUTOS E SERVIÇOS TERAPÊUTICOS PARA PREVENÇÃO E REABILITAÇÃO DA DOENÇA DE ALZHEIMER EM IDOSOS INSTITUCIONALIZADOS / [en] REMINDING ME OF MYSELF: THERAPEUTIC PRODUCTS AND SERVICES FOR PREVENTION AND RECOVERY OF THE ALZHEIMER S DISEASE AMONG INSTITUTIONALIZED ELDERLYALINE DE SOUZA ARIDE 06 April 2020 (has links)
[pt] Diante do cenário epidêmico das demências e do crescente envelhecimento populacional, esta pesquisa teve como foco o desenvolvimento de produtos e serviços reabilitadores e preventivos do Alzheimer para/com idosos institucionalizados. O objetivo do estudo foi melhorar a cognição e a qualidade de vida dos hóspedes, bem como valorizar seu papel social. Quanto à estrutura, a pesquisa se articulou em 5 etapas: (1) revisão bibliográfica sobre memória, processos cognitivos e Alzheimer; (2) estudo de caso no Bem Viver, que cumulou: observações das atividades, da rotina e das respostas dos idosos aos estímulos aplicados, entrevistas com os hóspedes, funcionários e familiares, e desenvolvimento de conceitos projetuais voltados à criação de produtos e serviços com foco no Alzheimer e na institucionalização; (3) cocriação de artefatos interdisciplinares e multifacetados em parceira com os profissionais da casa, amparada pela ferramenta Card Sorting e por um diagrama interdisciplinar; (4) implementação dos produtos e serviços pelos funcionários da casa nas atividades do Bem Viver; e (5) identificação dos resultados dos estímulos na cognição e na qualidade de vida dos idosos, mediante comparação dos dados coletados no momento inicial e final da pesquisa. No desfecho desta investigação, observou-se que os artefatos em formato aberto e as oficinas foram capazes de melhorar a orientação temporal e as habilidades de escrita e de cálculo de idosos, bem como permitiram despertar a criatividade dos hóspedes, fortalecer os laços de amizade e estimular memórias e funções mentais de indivíduos com os mais variados tipos de demência e perfis cognitivos. / [en] Taking into account the epidemic scenario of dementias and the increased growth of the elderly population, this research consisted of proposing products and services for both recovery and prevention of the Alzheimer s disease among institutionalized elderly. The aim of this study was to enhance cognition and the quality of life of patients, as well as promoting their social role. Regarding structure, this project was organized around 5 stages: (1) a bibliographic review on memory, cognitive processes and the Alzheimer s disease; (2) a case study at the nursing home Centro de Atividades Bem Viver that included observations of activities, routine, and the elderly responses to the stimuli applied; interviews with the guests, employees and relatives; and the development of design concepts for the creation of products and services that focused on the Alzheimer s disease and institutionalization; (3) cocreation of interdisciplinary and multifaceted artifacts in partnership with the instructors of the institution, as well as the support of Card Sorting and an interdisciplinary diagram; (4) implementation of products and services by the staff of the nursing home in the activities at Bem Viver; and (5) identification of results, with respect to cognition and quality of life, by drawing a comparison of the data gathered early and later on. At the end, it was possible to assess that the open-design objects and the workshops improved spatial orientation and also the elderly s writing and math skills, along with the guests creative awakening, the strengthening of friendship ties and the stimulation of memories and mental functions of individuals with different types of dementia and cognitive profiles.
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MULTISCALE SPATIOTEMPORAL MODELING FOR HUMAN DISEASE: AGENT BASED MODELS FOR NONTUBERCULOUS MYCOBACTERIUM INFECTIONS AND ALZHEIMER’S DISEASECatherine Weathered (13924857) 10 October 2022 (has links)
<p>Human disease and the corresponding immune response occur in three-dimensional space and time. Many diseases are difficult to study, either <em>in vivo</em> or <em>in vitro</em>, due to the complexity of the system. Despite computational models that can address complexity, many do not capture the spatial aspects of disease. Agent-based models are mechanistic, spatiotemporal computational models that can be integrated with other mathematical models to create multiscale models. Here I detail two models to examine spatiotemporal progression and possible treatment strategies for two diseases with low treatment success: <em>Mycobacterium avium complex</em> (MAC) and Alzheimer’s Disease.</p>
<p>MAC are biofilm-forming environmental microbes capable of residing in human lung nodules, causing MAC pulmonary disease (MAC-PD). Clinical drug susceptibility tests and treatment outcomes are poorly correlated, and nodules are complex and difficult to monitor, leading to low MAC cure rates (45-65%)<sup>2</sup>. I have developed an informative model of the initial infection events in MAC-PD. This model has been used to probe many different scenarios of infection and to predict the effect of potential interventions.</p>
<p>Alzheimer’s Disease (AD) is the leading cause of dementia, with no disease-altering pharmacological intervention. Microglia are phagocytotic neuroimmune cells, known to form barriers around plaques. There has been increased interest in leveraging microglia to slow the progression of neurodegeneration by manipulating these barriers. I present an agent-based model of microglia barriers at the single plaque level and use knock-out experiments to probe possible targets for immunotherapy and quantify their effects on plaque progression.</p>
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<b>Understanding the folding of amyloids using cryo-EM: </b><b><i>In vitro </i></b><b>studies and methods development</b>Ryan Patrick Kreiser (18405978) 18 April 2024 (has links)
<p dir="ltr">Neurodegenerative diseases are progressive, incurable conditions that affect tens of millions of people worldwide and are characterized by the aggregation of misfolded protein in the brain. Though the precise role of these amyloid aggregates in the onset and progression of these diseases is not clear at this time, there is a pressing need to understand how they form and spread in human disease. In service to these aims, I have conducted three small projects to expand knowledge in this regard. I first investigated the use of thioflavin T, a common amyloid stain, as an affinity reagent for the general purification of amyloid filaments from <i>ex vivo </i>samples, observing strong potential using a relatively simple, inexpensive magnetic bead conjugation technique. I next analyzed the formation of filaments of a truncated recombinant amyloid-beta peptide with residues 1-35, observing a new filament type formed at low pH in the wild-type sequence of this truncated peptide. Finally, I conducted structural studies on amyloid-beta(1-42) filaments prepared under different conditions consistent with traumatic brain injury to observe their effect on amyloid folding. While I found no effect of differential conditions on filament type, the low-resolution structures solved were highly consistent with aggregates found in Alzheimer’s disease patients, presenting a promising way forward for <i>in vitro</i> modeling of amyloid filaments that are true to pathology. In sum, the work here presented advances the concepts of both how amyloid aggregates from patient brains can be best prepared for structural analysis, and the factors underpinning their aggregation at the onset of neurodegenerative disease.</p>
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[pt] DESENVOLVIMENTO ADICIONAL DA NOVA GERAÇÃO DE N-ACILHIDRAZONAS CONTENDO O GRUPO 1-METILIMIDAZOL E SUA AVALIAÇÃO CONTRA MODELOS DE AGREGOPATIAS ENDÓCRINAS E NEUROENDÓCRINAS / [en] FURTHER DEVELOPMENT OF THE NEW GENERATION OF NACYLHYDRAZONES CONTAINING THE 1-METHYLIMIDAZOLE GROUP AND THEIR EVALUATION AGAINST MODELS OF ENDOCRINE AND NEUROENDOCRINE AGGREGOPATHIESALESSANDRA CARVALHO DE S E SILVA 20 August 2024 (has links)
[pt] O termo agregopatia é utilizado para definir doenças relacionadas ao
dobramento incorreto e consequente agregação patológica de proteínas. A doença
de Alzheimer (DA) caracteriza-se pela agregação do peptídeo (beta)-amiloide (A(beta)),
enquanto o diabetes mellitus tipo 2 (DMT2) está relacionado ao polipeptídeo
amiloide das ilhotas pancreáticas (IAPP). O dobramento defeituoso de proteínas e
peptídeos leva à formação de oligômeros solúveis e tóxicos, que eventualmente
acarretam morte celular. Além disto, ambas doenças apresentam uma componente
endócrina (ou neuroendócrina no caso da DA), devido ao papel da insulina em
suas fisiopatologias. Uma vez que a interação entre certos íons metálicos, como
cobre(II), e determinados peptídeos é considerada uma das causas agravantes da
agregação proteica, busca-se impedir ou atenuar as interações anômalas metalproteína através da utilização de metalóforos hidrazônicos. Estes são compostos
com afinidade moderada por biometais, desenvolvidos com o intuito de restaurar a
homeostase metálica e reduzir o estresse oxidativo presente nestas doenças. Neste
contexto, o presente trabalho descreve o desenvolvimento de dois novos
metalóforos cujas estruturas foram inspiradas em moléculas que se ligam a
receptores celulares: X1TMP (1-metil-1H-imidazol-2-carboxaldeído 3,4,5-
trimetoxibenzoíl hidrazona), baseado na mescalina, que se liga seletivamente à
receptores cerebrais, e X1NIC (1-metil-1H-imidazol-2-carboxaldeído nicotinoíl
hidrazona), pensado com base na estrutura da nicotina, que apresenta receptores
funcionais nas ilhotas pancreáticas e em células (beta). Na primeira parte do trabalho,
avaliou-se o potencial metalofórico do X1TMP frente a modelos biofísicos de
DA, utilizando o peptídeo A(beta)1-40 e seu fragmento coordenante A(beta)1-16,
comparando-o com seu derivado não-substituído X1Benz (1-metil-1H-imidazol2-carboxaldeído benzoíl hidrazona). Os valores de log P calculados e
experimentais foram semelhantes para ambos e dentro da faixa ideal e, de maneira
geral, todos os parâmetros físico-químicos avaliados estão de acordo com as
diretrizes para fármacos orais direcionados ao sistema nervoso central. A partir do
método de Job, foi verificado que ambas hidrazonas apresentaram interação com
cobre(II) com estequiometria do tipo ML. Os valores aparentes de log K foram de
5,74 mais ou menos 0,15 e 5,87 mais ou menos 0,11 para X1TMP e X1Benz respectivamente, indicando que
a presença das metoxilas não influencia na estabilidade do complexo formado.
Ambos os compostos foram capazes de diminuir a produção de espécies reativas
de oxigênio pelo sistema Cu(A(beta)) sob condições pseudo-fisiológicas, com o
X1TMP sendo ligeiramente mais eficaz do que o X1Benz. Além disto, as
hidrazonas foram capazes de inibir a agregação de A(beta) em condições equimolares
na presença e, surpreendentemente, na ausência de cobre(II). Utilizando a técnica
1H15N HSQC foi possível verificar que o X1Benz interage diretamente com o
peptídeo, o que justifica o efeito observado. Por outro lado, a inibição da
agregação mediada por cobre pode ocorrer através da formação de um complexo
ternário, como evidenciado por experimentos de 1H NMR. Na segunda parte do
trabalho, estudou-se o efeito do X1NIC no modelo de DMT2. Entretanto, uma
mistura de estereoisômeros geométricos foi obtida durante a síntese, o que
direcionou o estudo para comparação desses isômeros, e como ambos interagem
com o sistema Cu2+
‒hIAPP. Uma vez purificados e caracterizados, determinou-se
experimentalmente os valores de coeficiente de partição octanol-água
respectivamente como 0,62 mais ou menos 0,01 e 0,87 mais ou menos 0,02 para X1NIC-(E) e X1NIC-(Z).
Mais uma vez a afinidade aparente ligante-metal foi determinada, com valores de
log K = 5,82 mais ou menos 0,16 para o isômero tridentado (E) e 5,04 mais ou menos 0,04 para o isômero
bidentado (Z). O fragmento coordenante hIAPP18-22 foi utilizado para avaliar a
interação do peptídeo com o cobre(II) e o efeito dos ligantes neste sistema.
Através de experimentos de RMN de alto campo, a coordenação do tipo N3O foi
confirmada para o peptídeo, evidenciando a histidina como sítio de ancoragem do
metal. Ambos os isômeros formaram complexos ternários, embora com
estabilidades diferentes, conforme demonstrado tanto por RMN quanto por
voltametria cíclica. Por outro lado, a adição de um excesso de X1NIC-(E) se
mostrou eficaz na remoção de cobre ligado ao peptídeo, enquanto o mesmo não
foi observado para X1NIC-(Z), evidenciando a necessidade de um sítio tridentado
para uma boa ação metalofórica por parte destes ligantes. Vale ressaltar que
provavelmente os próprios complexos ternários sejam capazes de parcialmente
neutralizar os efeitos deletérios relacionados à química redox do metal. O presente
trabalho complementa o conhecimento acerca da nova geração de metalóforos
hidrazônicos contendo 1-metilimidazol, trazendo novas perspectivas para suas
aplicações em futuros trabalhos direcionados tanto para DA quanto para o DMT2. / [en] Both Alzheimer s disease (AD) and type-2 diabetes mellitus (T2DM) are
considered metal-enhanced aggregopathies, in which the anomalous interactions
between copper(II) and the A(beta) and IAPP peptides, respectively, lead to protein
misfolding, aggregation and oxidative stress. In this scenario, our research group
proposed the use of 1-methylimidazole-containing N-acylhydrazones as
metallophores, aiming to compete with the interaction of this metal ion with
amyloidogenic proteins, intervening in the process of aggregation and restoring
metal homeostasis. In the present work, two new compounds of this series were
proposed, based on the structure of mescaline and nicotine: X1TMP and X1NIC.
The first was evaluated in biophysical models of AD using the A(beta)1-40 peptide and
its fragment A(beta)1-16 and was compared to its unsubstituted analogue X1Benz.
X1NIC, on the other hand, was synthesized separately as its (E) and (Z) isomers,
and they were in turn studied using the coordinating hIAPP18-22 fragment in the
context of T2DM. X1TMP and X1Benz were both able to lessen the coppermediated production of ROS and prevent A(beta) aggregation in the presence and
absence of this metal. The formation of ternary species with different stabilities
was clearly demonstrated for the studied compounds in both AD and T2DM
systems using different techniques. In the case of T2DM, however, only X1NIC-
(E) seemed able to remove copper(II) from hIAPP18-22 at ligand excess conditions,
which is consistent with its higher affinity for this ion. It is worth mentioning that
all tridentate hydrazones [X1TMP, X1Benz and X1NIC-(E)] presented similar,
moderate, apparent affinity constant values, while X1NIC-(Z) had a weaker
interaction with copper since it performs as a bidentate ligand. In general, these
new compounds demonstrated promising metallophoric activity and proved ability
to interfere with the anomalous copper-peptide interactions. It is possible that the
ternary species are enough to partially passivate the metal, avoiding deleterious
redox cycling effects.
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