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The toxicity of alpha-syn condensates in the presence and absence of metal ions

Bibliographic Details
Main Author: Pinto, Miriam dos Santos
Publication Date: 2024
Format: Master thesis
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10400.5/95870
Summary: Tese de mestrado, Bioquímica e Biomedicina, 2024, Universidade de Lisboa, Faculdade de Ciências
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spelling The toxicity of alpha-syn condensates in the presence and absence of metal ionsAlfa-sinucleínaDoença de ParkinsonSeparação de Fases LíquidasNeurodegeneraçãoIões metálicosTeses de mestrado - 2024Departamento de Química e BioquímicaTese de mestrado, Bioquímica e Biomedicina, 2024, Universidade de Lisboa, Faculdade de CiênciasNeurodegenerative diseases (NDDs), characterized by progressive neuronal death and misfolded protein aggregation, pose significant clinical, social, and personal challenges. Parkinson's Disease (PD), the second most common neurological disorder, is notably associated with the aggregation of alpha-synuclein (aSyn). Despite its prominence, the transition of monomeric aSyn to aggregates remains inadequately understood. Recent studies suggest that Liquid-Liquid Phase Separation (LLPS) and disease related metal ions involve the transition in the molecular pathogenesis of PD. LLPS involves the separation of biomolecules into distinct phases without a membrane, potentially facilitating aSyn aggregation through dynamic condensates that eventually form solid deposits. I aim to investigate LLPS of aSyn and macroscopy dynamics of its formed droplets over time, and examine how PD related metal ions, affect the dynamic process of LLPS and modulate its toxicity to neuroblastoma cells. These metal ions, prevalent in the brain and specifically interacting with aSyn are presumably modulating LLPS, toxicity and aggregation of aSyn, making it crucial to understand their roles in the molecular pathogenesis of PD I expressed α-synuclein (aSyn) proteins in E. coli and studied the biophysical properties and toxicities of aSyn-metal ion coacervates using various techniques, including a protein crystallization robotic dispenser and confocal microscopy. In the presence of metal ions such as CuCl₂, MnCl₂, ZnCl₂, and FeCl₃, the number of droplets significantly decreased. I found that CuCl₂ ions immobilize aSyn condensates and increase their toxicity. In contrast, MnCl₂, ZnCl₂, and FeCl₃ help maintain a longer metastable state of the condensates, reducing their toxicity This project highlights the crucial role of metal ions in modulating aSyn phase behavior, condensate toxicity and their potential involvement in the progression of PD.Jinghui, LuoGomes, Cláudio MRepositório da Universidade de LisboaPinto, Miriam dos Santos2024-12-02T18:48:16Z202420242024-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10400.5/95870enginfo:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-17T16:29:11Zoai:repositorio.ulisboa.pt:10400.5/95870Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T04:16:34.671400Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv The toxicity of alpha-syn condensates in the presence and absence of metal ions
title The toxicity of alpha-syn condensates in the presence and absence of metal ions
spellingShingle The toxicity of alpha-syn condensates in the presence and absence of metal ions
Pinto, Miriam dos Santos
Alfa-sinucleína
Doença de Parkinson
Separação de Fases Líquidas
Neurodegeneração
Iões metálicos
Teses de mestrado - 2024
Departamento de Química e Bioquímica
title_short The toxicity of alpha-syn condensates in the presence and absence of metal ions
title_full The toxicity of alpha-syn condensates in the presence and absence of metal ions
title_fullStr The toxicity of alpha-syn condensates in the presence and absence of metal ions
title_full_unstemmed The toxicity of alpha-syn condensates in the presence and absence of metal ions
title_sort The toxicity of alpha-syn condensates in the presence and absence of metal ions
author Pinto, Miriam dos Santos
author_facet Pinto, Miriam dos Santos
author_role author
dc.contributor.none.fl_str_mv Jinghui, Luo
Gomes, Cláudio M
Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Pinto, Miriam dos Santos
dc.subject.por.fl_str_mv Alfa-sinucleína
Doença de Parkinson
Separação de Fases Líquidas
Neurodegeneração
Iões metálicos
Teses de mestrado - 2024
Departamento de Química e Bioquímica
topic Alfa-sinucleína
Doença de Parkinson
Separação de Fases Líquidas
Neurodegeneração
Iões metálicos
Teses de mestrado - 2024
Departamento de Química e Bioquímica
description Tese de mestrado, Bioquímica e Biomedicina, 2024, Universidade de Lisboa, Faculdade de Ciências
publishDate 2024
dc.date.none.fl_str_mv 2024-12-02T18:48:16Z
2024
2024
2024-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.5/95870
url http://hdl.handle.net/10400.5/95870
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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