Efeito neuroprotetor da lectina de Canavalia ensiformis (ConA) via sítio de ligação a aminoácidos em células da linhagem PC12 Adh

Detalhes bibliográficos
Ano de defesa: 2025
Autor(a) principal: Roma, Renato Rodrigues
Orientador(a): Teixeira, Claudener Souza
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Área do conhecimento CNPq:
Link de acesso: http://repositorio.ufc.br/handle/riufc/81556
Resumo: Glutamate, the main excitatory neurotransmitter in the central nervous system, plays a crucial role in various physiological functions. However, excess glutamate in the synaptic cleft induces excitotoxicity, a process associated with several neuropathological diseases and conditions. The search for drugs from bioactive plant compounds, such as lectins, becomes essential for human well-being. Lectins, proteins that specifically and reversibly bind to carbohydrates and glycoconjugates, demonstrate promising activities in the central nervous system, such as antioxidant, anti-inflammatory, and neuroprotective effects. However, their neuroprotective mechanisms focus only on the carbohydrate-recognition domain, neglecting other binding sites. Therefore, this study investigated the in vitro neuroprotective effect of Canavalia ensiformis lectin - ConA in PC12 cells and its in silico interaction with glutamate through a site different from the carbohydrate-recognition domain. ConA was tested for neuroprotection against glutamate-induced toxicity in PC12 cells using MTT assays. Fluorescence spectroscopy and molecular docking techniques were used to evaluate the interaction and affinity between ConA and glutamate. The results revealed that the neuroprotective effect of ConA is not dose- dependent and is independent of its carbohydrate-recognition domain. The mechanism of action discovered involves the direct sequestration of glutamate through ConA's amino acid binding site. Spectroscopy and molecular docking analyses confirmed this interaction through this hydrophobic site. These findings expand the therapeutic potential of plant lectins in the treatment of central nervous system diseases, opening new perspectives for the development of more targeted and innovative therapies.
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spelling Roma, Renato RodriguesTeixeira, Claudener Souza2025-07-14T18:13:30Z2025-07-14T18:13:30Z2025ROMA, Renato Rodrigues. Efeito neuroprotetor da lectina de Canavalia ensiformis (ConA) via sítio de ligação a aminoácidos em células da linhagem PC12 Adh. 2025. Tese (Doutorado em Bioquímica) - Universidade Federal do Ceará, Fortaleza, 2025.http://repositorio.ufc.br/handle/riufc/81556Glutamate, the main excitatory neurotransmitter in the central nervous system, plays a crucial role in various physiological functions. However, excess glutamate in the synaptic cleft induces excitotoxicity, a process associated with several neuropathological diseases and conditions. The search for drugs from bioactive plant compounds, such as lectins, becomes essential for human well-being. Lectins, proteins that specifically and reversibly bind to carbohydrates and glycoconjugates, demonstrate promising activities in the central nervous system, such as antioxidant, anti-inflammatory, and neuroprotective effects. However, their neuroprotective mechanisms focus only on the carbohydrate-recognition domain, neglecting other binding sites. Therefore, this study investigated the in vitro neuroprotective effect of Canavalia ensiformis lectin - ConA in PC12 cells and its in silico interaction with glutamate through a site different from the carbohydrate-recognition domain. ConA was tested for neuroprotection against glutamate-induced toxicity in PC12 cells using MTT assays. Fluorescence spectroscopy and molecular docking techniques were used to evaluate the interaction and affinity between ConA and glutamate. The results revealed that the neuroprotective effect of ConA is not dose- dependent and is independent of its carbohydrate-recognition domain. The mechanism of action discovered involves the direct sequestration of glutamate through ConA's amino acid binding site. Spectroscopy and molecular docking analyses confirmed this interaction through this hydrophobic site. These findings expand the therapeutic potential of plant lectins in the treatment of central nervous system diseases, opening new perspectives for the development of more targeted and innovative therapies.O glutamato, principal neurotransmissor excitatório do sistema nervoso central, desempenha um papel crucial em diversas funções fisiológicas. No entanto, o excesso de glutamato na fenda sináptica induz a excitotoxicidade, um processo associado a várias doenças e condições neuropatológicas. A busca por medicamentos em compostos bioativos de plantas, como as lectinas, torna-se essencial para o bem-estar humano. As lectinas, proteínas que se ligam especificamente e reversivelmente a carboidratos e glicoconjugados, demonstram atividades promissoras ao sistema nervoso central como, antioxidantes, anti-inflamatórias e neuroprotetoras. Contudo, seus mecanismos neuroprotetores focam apenas no domínio de reconhecimento a carboidratos, negligenciando outros sítios de ligação. Por isso, este estudo investigou o efeito neuroprotetor in vitro da lectina de Canavalia ensiformis - ConA em células PC12 e in silico sua interação com glutamato através de um sitio diferente do domínio de reconhecimento a carboidratos. A ConA foi testada quanto à neuroproteção contra a toxicidade induzida por glutamato em células PC12 utilizando ensaios de MTT. Técnicas de espectroscopia de fluorescência e docking molecular foram utilizadas para avaliar a interação e a afinidade entre a ConA e o glutamato. Os resultados revelaram que o efeito neuroprotetor da ConA, não é dose-dependente e independe do seu domínio de reconhecimento a carboidratos. O mecanismo de ação descoberto envolve o sequestro direto do glutamato através do sítio de ligação a aminoácidos da ConA. As análises de espectroscopia e docking molecular confirmaram essa interação por este sítio hidrofóbico. Essas descobertas ampliam o potencial terapêutico das lectinas vegetais no tratamento de doenças do sistema nervoso central, abrindo novas perspectivas para o desenvolvimento de terapias mais direcionadas e inovadoras.Efeito neuroprotetor da lectina de Canavalia ensiformis (ConA) via sítio de ligação a aminoácidos em células da linhagem PC12 AdhNeuroprotective effect of canavalia ensiformis lectin (ConAa) via amino acid binding site in PC12 ADH cell lineinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisExcitotoxicidadeNeuroproteçãoSítio de ligação a aminoácidosPC12LectinaExcitotoxicityNeuroprotectionAmino acid binding sitePC12LectinCNPQ::CIENCIAS BIOLOGICASinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFChttp://lattes.cnpq.br/2125864440997281http://lattes.cnpq.br/07288010462724322025-07-14ORIGINAL2025_tese_rrroma.pdf2025_tese_rrroma.pdfapplication/pdf1957128http://repositorio.ufc.br/bitstream/riufc/81556/3/2025_tese_rrroma.pdf34ddbda7af7b14099e5ff4e101908d37MD53LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/81556/4/license.txt8a4605be74aa9ea9d79846c1fba20a33MD54riufc/815562025-07-14 15:13:33.11oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2025-07-14T18:13:33Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Efeito neuroprotetor da lectina de Canavalia ensiformis (ConA) via sítio de ligação a aminoácidos em células da linhagem PC12 Adh
dc.title.en.pt_BR.fl_str_mv Neuroprotective effect of canavalia ensiformis lectin (ConAa) via amino acid binding site in PC12 ADH cell line
title Efeito neuroprotetor da lectina de Canavalia ensiformis (ConA) via sítio de ligação a aminoácidos em células da linhagem PC12 Adh
spellingShingle Efeito neuroprotetor da lectina de Canavalia ensiformis (ConA) via sítio de ligação a aminoácidos em células da linhagem PC12 Adh
Roma, Renato Rodrigues
CNPQ::CIENCIAS BIOLOGICAS
Excitotoxicidade
Neuroproteção
Sítio de ligação a aminoácidos
PC12
Lectina
Excitotoxicity
Neuroprotection
Amino acid binding site
PC12
Lectin
title_short Efeito neuroprotetor da lectina de Canavalia ensiformis (ConA) via sítio de ligação a aminoácidos em células da linhagem PC12 Adh
title_full Efeito neuroprotetor da lectina de Canavalia ensiformis (ConA) via sítio de ligação a aminoácidos em células da linhagem PC12 Adh
title_fullStr Efeito neuroprotetor da lectina de Canavalia ensiformis (ConA) via sítio de ligação a aminoácidos em células da linhagem PC12 Adh
title_full_unstemmed Efeito neuroprotetor da lectina de Canavalia ensiformis (ConA) via sítio de ligação a aminoácidos em células da linhagem PC12 Adh
title_sort Efeito neuroprotetor da lectina de Canavalia ensiformis (ConA) via sítio de ligação a aminoácidos em células da linhagem PC12 Adh
author Roma, Renato Rodrigues
author_facet Roma, Renato Rodrigues
author_role author
dc.contributor.author.fl_str_mv Roma, Renato Rodrigues
dc.contributor.advisor1.fl_str_mv Teixeira, Claudener Souza
contributor_str_mv Teixeira, Claudener Souza
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS BIOLOGICAS
topic CNPQ::CIENCIAS BIOLOGICAS
Excitotoxicidade
Neuroproteção
Sítio de ligação a aminoácidos
PC12
Lectina
Excitotoxicity
Neuroprotection
Amino acid binding site
PC12
Lectin
dc.subject.ptbr.pt_BR.fl_str_mv Excitotoxicidade
Neuroproteção
Sítio de ligação a aminoácidos
PC12
Lectina
dc.subject.en.pt_BR.fl_str_mv Excitotoxicity
Neuroprotection
Amino acid binding site
PC12
Lectin
description Glutamate, the main excitatory neurotransmitter in the central nervous system, plays a crucial role in various physiological functions. However, excess glutamate in the synaptic cleft induces excitotoxicity, a process associated with several neuropathological diseases and conditions. The search for drugs from bioactive plant compounds, such as lectins, becomes essential for human well-being. Lectins, proteins that specifically and reversibly bind to carbohydrates and glycoconjugates, demonstrate promising activities in the central nervous system, such as antioxidant, anti-inflammatory, and neuroprotective effects. However, their neuroprotective mechanisms focus only on the carbohydrate-recognition domain, neglecting other binding sites. Therefore, this study investigated the in vitro neuroprotective effect of Canavalia ensiformis lectin - ConA in PC12 cells and its in silico interaction with glutamate through a site different from the carbohydrate-recognition domain. ConA was tested for neuroprotection against glutamate-induced toxicity in PC12 cells using MTT assays. Fluorescence spectroscopy and molecular docking techniques were used to evaluate the interaction and affinity between ConA and glutamate. The results revealed that the neuroprotective effect of ConA is not dose- dependent and is independent of its carbohydrate-recognition domain. The mechanism of action discovered involves the direct sequestration of glutamate through ConA's amino acid binding site. Spectroscopy and molecular docking analyses confirmed this interaction through this hydrophobic site. These findings expand the therapeutic potential of plant lectins in the treatment of central nervous system diseases, opening new perspectives for the development of more targeted and innovative therapies.
publishDate 2025
dc.date.accessioned.fl_str_mv 2025-07-14T18:13:30Z
dc.date.available.fl_str_mv 2025-07-14T18:13:30Z
dc.date.issued.fl_str_mv 2025
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv ROMA, Renato Rodrigues. Efeito neuroprotetor da lectina de Canavalia ensiformis (ConA) via sítio de ligação a aminoácidos em células da linhagem PC12 Adh. 2025. Tese (Doutorado em Bioquímica) - Universidade Federal do Ceará, Fortaleza, 2025.
dc.identifier.uri.fl_str_mv http://repositorio.ufc.br/handle/riufc/81556
identifier_str_mv ROMA, Renato Rodrigues. Efeito neuroprotetor da lectina de Canavalia ensiformis (ConA) via sítio de ligação a aminoácidos em células da linhagem PC12 Adh. 2025. Tese (Doutorado em Bioquímica) - Universidade Federal do Ceará, Fortaleza, 2025.
url http://repositorio.ufc.br/handle/riufc/81556
dc.language.iso.fl_str_mv por
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dc.source.none.fl_str_mv reponame:Repositório Institucional da Universidade Federal do Ceará (UFC)
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