Publicação
Engineering of a fluorescent bacteriophage for amyloid-β oligomers detection
| Resumo: | Alzheimer's disease was first described in 1907 by Dr. Alöis Alzheimer in Frankfurt. Since then, Alzheimer's has become the leading cause of dementia worldwide. This disease is currently characterized by a set of cognitive, behavioural, physiological, physical, and other symptoms, such as short-term memory loss, impulsivity, depression, visuospatial problems and sleep disorders, among others. Two biomarkers have been identified for Alzheimer's disease, namely amyloid-β and Tau proteins. Both appear to be related with the disease development, but their role is not yet fully understood. Various explanations for the function of each protein during the development of the disease have already been put forward, but no theory has yet been definitively proven. Nevertheless, it is known that the accumulation of amyloid-β in the brain can begin up to 20 years before the onset of cognitive decline. The diagnosis of Alzheimer's remains fundamentally a clinical diagnosis, in which the patient must present with symptoms of the disease for it to be diagnosed, where irreversible brain damage has already occurred. It is therefore imperative to create a method capable of diagnosing Alzheimer's disease in advance, based on the biomarkers of the disease. To this end, this study focused on the development of chemically modified bacteriophages (phages), using the previously genetically engineered phages with a fluorochrome attached to the surface of the phage for the early detection of amyloid-β oligomers. In this way, it was possible to optimize the phage labelling protocol, testing various parameters of the process, such as the method of purifying the labelled phages, fluorochrome concentration, agitation during the reaction and reaction time. The permeability of the fluorescent phages through the blood-brain barrier was also tested, proving that the permeability decreases when compared to the non-fluorescent phages, however, tests on animal models are necessary to better prove this result, additionally, it was demonstrated that the integrity of the barrier was not compromised by the presence of the phages. |
|---|---|
| Autores principais: | Silva, Pedro Francisco Costa da |
| Assunto: | Alzheimer’s disease Bacteriophages Blood-brain barrier Early diagnosis Fluorescent phage NIR fluorochrome Bacteriófagos Barreira hematoencefálica Diagnóstico precoce Doença de Alzheimer Fagos fluorescentes Fluorocromo NIR |
| Ano: | 2023 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso embargado |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1866877959962361856 |
|---|---|
| author | Silva, Pedro Francisco Costa da |
| author_facet | Silva, Pedro Francisco Costa da |
| author_role | author |
| contributor_name_str_mv | Martins, Ivone M. Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Silva, Pedro Francisco Costa da\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Martins, Ivone M. Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Silva, Pedro Francisco Costa da |
| datacite.date.Accepted.fl_str_mv | 2023-11-22T00:00:00Z |
| datacite.date.embargoed.fl_str_mv | 10000-01-01T00:00:00Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_f1cf |
| datacite.subjects.subject.fl_str_mv | Alzheimer’s disease Bacteriophages Blood-brain barrier Early diagnosis Fluorescent phage NIR fluorochrome Bacteriófagos Barreira hematoencefálica Diagnóstico precoce Doença de Alzheimer Fagos fluorescentes Fluorocromo NIR |
| datacite.titles.title.fl_str_mv | Engineering of a fluorescent bacteriophage for amyloid-β oligomers detection |
| dc.contributor.none.fl_str_mv | Martins, Ivone M. Universidade do Minho |
| dc.creator.none.fl_str_mv | Silva, Pedro Francisco Costa da |
| dc.date.Accepted.fl_str_mv | 2023-11-22T00:00:00Z |
| dc.date.embargoed.fl_str_mv | 10000-01-01T00:00:00Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/88155 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.cclincense.fl_str_mv | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_f1cf |
| dc.rights.rights.copyright.fl_str_mv | closedAccess |
| dc.subject.none.fl_str_mv | Alzheimer’s disease Bacteriophages Blood-brain barrier Early diagnosis Fluorescent phage NIR fluorochrome Bacteriófagos Barreira hematoencefálica Diagnóstico precoce Doença de Alzheimer Fagos fluorescentes Fluorocromo NIR |
| dc.title.fl_str_mv | Engineering of a fluorescent bacteriophage for amyloid-β oligomers detection |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_bdcc |
| description | Alzheimer's disease was first described in 1907 by Dr. Alöis Alzheimer in Frankfurt. Since then, Alzheimer's has become the leading cause of dementia worldwide. This disease is currently characterized by a set of cognitive, behavioural, physiological, physical, and other symptoms, such as short-term memory loss, impulsivity, depression, visuospatial problems and sleep disorders, among others. Two biomarkers have been identified for Alzheimer's disease, namely amyloid-β and Tau proteins. Both appear to be related with the disease development, but their role is not yet fully understood. Various explanations for the function of each protein during the development of the disease have already been put forward, but no theory has yet been definitively proven. Nevertheless, it is known that the accumulation of amyloid-β in the brain can begin up to 20 years before the onset of cognitive decline. The diagnosis of Alzheimer's remains fundamentally a clinical diagnosis, in which the patient must present with symptoms of the disease for it to be diagnosed, where irreversible brain damage has already occurred. It is therefore imperative to create a method capable of diagnosing Alzheimer's disease in advance, based on the biomarkers of the disease. To this end, this study focused on the development of chemically modified bacteriophages (phages), using the previously genetically engineered phages with a fluorochrome attached to the surface of the phage for the early detection of amyloid-β oligomers. In this way, it was possible to optimize the phage labelling protocol, testing various parameters of the process, such as the method of purifying the labelled phages, fluorochrome concentration, agitation during the reaction and reaction time. The permeability of the fluorescent phages through the blood-brain barrier was also tested, proving that the permeability decreases when compared to the non-fluorescent phages, however, tests on animal models are necessary to better prove this result, additionally, it was demonstrated that the integrity of the barrier was not compromised by the presence of the phages. |
| dirty | 0 |
| eu_rights_str_mv | embargoedAccess |
| format | masterThesis |
| fulltext.url.fl_str_mv | https://repositorium.uminho.pt/bitstreams/9a9c7099-91d9-47d0-9a39-76ba33347131/download |
| id | rum_115f0391f77e50ada188c19f67140fdb |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/88155 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/88155 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Silva, Pedro Francisco Costa da |
| publishDate | 2023 |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engporAlzheimer's disease was first described in 1907 by Dr. Alöis Alzheimer in Frankfurt. Since then, Alzheimer's has become the leading cause of dementia worldwide. This disease is currently characterized by a set of cognitive, behavioural, physiological, physical, and other symptoms, such as short-term memory loss, impulsivity, depression, visuospatial problems and sleep disorders, among others. Two biomarkers have been identified for Alzheimer's disease, namely amyloid-β and Tau proteins. Both appear to be related with the disease development, but their role is not yet fully understood. Various explanations for the function of each protein during the development of the disease have already been put forward, but no theory has yet been definitively proven. Nevertheless, it is known that the accumulation of amyloid-β in the brain can begin up to 20 years before the onset of cognitive decline. The diagnosis of Alzheimer's remains fundamentally a clinical diagnosis, in which the patient must present with symptoms of the disease for it to be diagnosed, where irreversible brain damage has already occurred. It is therefore imperative to create a method capable of diagnosing Alzheimer's disease in advance, based on the biomarkers of the disease. To this end, this study focused on the development of chemically modified bacteriophages (phages), using the previously genetically engineered phages with a fluorochrome attached to the surface of the phage for the early detection of amyloid-β oligomers. In this way, it was possible to optimize the phage labelling protocol, testing various parameters of the process, such as the method of purifying the labelled phages, fluorochrome concentration, agitation during the reaction and reaction time. The permeability of the fluorescent phages through the blood-brain barrier was also tested, proving that the permeability decreases when compared to the non-fluorescent phages, however, tests on animal models are necessary to better prove this result, additionally, it was demonstrated that the integrity of the barrier was not compromised by the presence of the phages.application/pdfporEngineering of a fluorescent bacteriophage for amyloid-β oligomers detectionSilva, Pedro Francisco Costa daMartins, Ivone M.HostingInstitutionOrganizationalUniversidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptURNurn:tid:2034700872023-11-222023-1010000-01-01T00:00:00Z2023-11-22T00:00:00ZHandlehttps://hdl.handle.net/1822/88155http://purl.org/coar/access_right/c_f1cfembargoed accessAlzheimer’s diseaseBacteriophagesBlood-brain barrierEarly diagnosisFluorescent phageNIR fluorochromeBacteriófagosBarreira hematoencefálicaDiagnóstico precoceDoença de AlzheimerFagos fluorescentesFluorocromo NIR2025700 bytesliteraturehttp://purl.org/coar/resource_type/c_bdccmaster thesis2023-11-22http://creativecommons.org/licenses/by-nc-nd/4.0/closedAccesshttp://purl.org/coar/access_right/c_f1cfapplication/pdffulltexthttps://repositorium.uminho.pt/bitstreams/9a9c7099-91d9-47d0-9a39-76ba33347131/download |
| spellingShingle | Engineering of a fluorescent bacteriophage for amyloid-β oligomers detection Silva, Pedro Francisco Costa da Alzheimer’s disease Bacteriophages Blood-brain barrier Early diagnosis Fluorescent phage NIR fluorochrome Bacteriófagos Barreira hematoencefálica Diagnóstico precoce Doença de Alzheimer Fagos fluorescentes Fluorocromo NIR |
| status | SINGLETON |
| subject.fl_str_mv | Alzheimer’s disease Bacteriophages Blood-brain barrier Early diagnosis Fluorescent phage NIR fluorochrome Bacteriófagos Barreira hematoencefálica Diagnóstico precoce Doença de Alzheimer Fagos fluorescentes Fluorocromo NIR |
| title | Engineering of a fluorescent bacteriophage for amyloid-β oligomers detection |
| title_full | Engineering of a fluorescent bacteriophage for amyloid-β oligomers detection |
| title_fullStr | Engineering of a fluorescent bacteriophage for amyloid-β oligomers detection |
| title_full_unstemmed | Engineering of a fluorescent bacteriophage for amyloid-β oligomers detection |
| title_short | Engineering of a fluorescent bacteriophage for amyloid-β oligomers detection |
| title_sort | Engineering of a fluorescent bacteriophage for amyloid-β oligomers detection |
| topic | Alzheimer’s disease Bacteriophages Blood-brain barrier Early diagnosis Fluorescent phage NIR fluorochrome Bacteriófagos Barreira hematoencefálica Diagnóstico precoce Doença de Alzheimer Fagos fluorescentes Fluorocromo NIR |
| topic_facet | Alzheimer’s disease Bacteriophages Blood-brain barrier Early diagnosis Fluorescent phage NIR fluorochrome Bacteriófagos Barreira hematoencefálica Diagnóstico precoce Doença de Alzheimer Fagos fluorescentes Fluorocromo NIR |
| url | https://hdl.handle.net/1822/88155 |
| visible | 1 |