Unraveling the axonal proteome of hippocampal neurons

Detalhes bibliográficos
Autor(a) principal: Felgueiras, José João Macedo
Data de Publicação: 2021
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10773/30915
Resumo: Axons are long projections of a nerve cell responsible to conduct electrochemical impulses. The length of axons, their morphological complexity long axonas and neuronal plasticity poses a challenge to maintain cellular function. Transport along the neurons can address the mentioned hurdles. However, this cellular mechanism has some drawbacks associated, such as the long time to transport cargos from one point to another due to the neuronal size and architecture. Nowadays, a synergy between axonal transport and local translation is well accepted, both working tightly to regulate the axonal proteome. Therefore, these mechanisms have a crucial role in vital axonal functions, such as synaptic plasticity, axonal pathfinding, and regeneration. The axonal proteome is composed of the entire repertoire of the present proteins. in the axons at a given moment, and is in a continuous and dynamic changing process. Although great efforts have been made, the majority of studies available in literature use transcriptomic techniques, which can significantly differ from protein cell expression. In the present study, we reported for the first time the axonal proteome in developing hippocampal rat neurons. Additionally, to gain a systemic understanding of the functional and dynamic role of these proteins, we perform a high-throughput analysis, using multiple bioinformatic tools to catalogue and extensively characterize the axonal proteome. In addition, we run an enrichment analysis and search for different neurological disorders fingerprints among the proteome, using several databases to create a disease-association profile, and ultimately identify possible future research candidates to integrate in clinical translation.
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spelling Unraveling the axonal proteome of hippocampal neuronsAxonal proteomeLocal protein synthesisQuantitative proteomicsBioinformatic analysisNeurological disordersAxons are long projections of a nerve cell responsible to conduct electrochemical impulses. The length of axons, their morphological complexity long axonas and neuronal plasticity poses a challenge to maintain cellular function. Transport along the neurons can address the mentioned hurdles. However, this cellular mechanism has some drawbacks associated, such as the long time to transport cargos from one point to another due to the neuronal size and architecture. Nowadays, a synergy between axonal transport and local translation is well accepted, both working tightly to regulate the axonal proteome. Therefore, these mechanisms have a crucial role in vital axonal functions, such as synaptic plasticity, axonal pathfinding, and regeneration. The axonal proteome is composed of the entire repertoire of the present proteins. in the axons at a given moment, and is in a continuous and dynamic changing process. Although great efforts have been made, the majority of studies available in literature use transcriptomic techniques, which can significantly differ from protein cell expression. In the present study, we reported for the first time the axonal proteome in developing hippocampal rat neurons. Additionally, to gain a systemic understanding of the functional and dynamic role of these proteins, we perform a high-throughput analysis, using multiple bioinformatic tools to catalogue and extensively characterize the axonal proteome. In addition, we run an enrichment analysis and search for different neurological disorders fingerprints among the proteome, using several databases to create a disease-association profile, and ultimately identify possible future research candidates to integrate in clinical translation.Os axónios são longas projeções das células nervosas, responsáveis por conduzem impulsos elétrico-químicos. Tanto a longa extensão que os axónios podem atingir, como também a complexidade morfológica e plasticidade neuronal, tornam especialmente desafiante para os neurónios a manutenção de uma função adequada. O transporte ao longo dos neurónios vem dar resposta às necessidades supramencionadas. No entanto, este mecanismo celular enfrenta ainda alguns obstáculos, como os longos períodos de tempo que as cargas levam a ser transportadas, tendo em conta a dimensão e arquitetura neuronal. Hoje em dia, é já aceite uma sinergia entre o transporte axonal e a tradução local, que atuam estreitamente para regular o proteoma axonal e, por conseguinte, funções axonais vitais, como a plasticidade sináptica, regeneração neuronal e projeções axonais. Assim, o proteoma axonal é composto pelo reportório das proteínas presentes nos axónios num determinado momento, estando estas também sujeitas a um processo contínuo e dinâmico de mudança. Embora grandes esforços tenham vindo a ser feitos, a maioria dos estudos disponíveis na literatura utilizam técnicas transcriptómicas, que podem diferir significativamente da expressão celular proteica. Neste estudo, descrevemos pela primeira vez o proteoma axonal em neurónios do hipocampo de rato. Adicionalmente, para obter uma compreensão sistemática e funcional das proteínas presentes no axónio, realizamos uma análise de alto rendimento recorrendo a várias ferramentas de bioinformática para catalogar e caracterizar extensivamente o proteoma axonal dos neurónios do hipocampo. Além disso, executamos uma análise de enriquecimento de dados e investigamos o fingerprints de diferentes doenças neurológicas, usando várias bases de dados. Desta forma permitiu-nos criar um perfil de associação de doenças com o proteoma axonal com vista a identificar possíveis futuros candidatos de pesquisa ou translação clínica.2023-03-01T00:00:00Z2021-02-23T00:00:00Z2021-02-23info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/30915engFelgueiras, José João Macedoinfo:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T11:59:45Zoai:ria.ua.pt:10773/30915Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:02:56.238703Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Unraveling the axonal proteome of hippocampal neurons
title Unraveling the axonal proteome of hippocampal neurons
spellingShingle Unraveling the axonal proteome of hippocampal neurons
Felgueiras, José João Macedo
Axonal proteome
Local protein synthesis
Quantitative proteomics
Bioinformatic analysis
Neurological disorders
title_short Unraveling the axonal proteome of hippocampal neurons
title_full Unraveling the axonal proteome of hippocampal neurons
title_fullStr Unraveling the axonal proteome of hippocampal neurons
title_full_unstemmed Unraveling the axonal proteome of hippocampal neurons
title_sort Unraveling the axonal proteome of hippocampal neurons
author Felgueiras, José João Macedo
author_facet Felgueiras, José João Macedo
author_role author
dc.contributor.author.fl_str_mv Felgueiras, José João Macedo
dc.subject.por.fl_str_mv Axonal proteome
Local protein synthesis
Quantitative proteomics
Bioinformatic analysis
Neurological disorders
topic Axonal proteome
Local protein synthesis
Quantitative proteomics
Bioinformatic analysis
Neurological disorders
description Axons are long projections of a nerve cell responsible to conduct electrochemical impulses. The length of axons, their morphological complexity long axonas and neuronal plasticity poses a challenge to maintain cellular function. Transport along the neurons can address the mentioned hurdles. However, this cellular mechanism has some drawbacks associated, such as the long time to transport cargos from one point to another due to the neuronal size and architecture. Nowadays, a synergy between axonal transport and local translation is well accepted, both working tightly to regulate the axonal proteome. Therefore, these mechanisms have a crucial role in vital axonal functions, such as synaptic plasticity, axonal pathfinding, and regeneration. The axonal proteome is composed of the entire repertoire of the present proteins. in the axons at a given moment, and is in a continuous and dynamic changing process. Although great efforts have been made, the majority of studies available in literature use transcriptomic techniques, which can significantly differ from protein cell expression. In the present study, we reported for the first time the axonal proteome in developing hippocampal rat neurons. Additionally, to gain a systemic understanding of the functional and dynamic role of these proteins, we perform a high-throughput analysis, using multiple bioinformatic tools to catalogue and extensively characterize the axonal proteome. In addition, we run an enrichment analysis and search for different neurological disorders fingerprints among the proteome, using several databases to create a disease-association profile, and ultimately identify possible future research candidates to integrate in clinical translation.
publishDate 2021
dc.date.none.fl_str_mv 2021-02-23T00:00:00Z
2021-02-23
2023-03-01T00:00:00Z
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