Detalhes bibliográficos
| Resumo: | Alpha-Synuclein (αS) is a small intrinsically disordered protein (IDP) abundantly ex- pressed in presynaptic terminals of neurons that displays a highly amyloidogenic nature. Pathological conditions can trigger the transition of soluble αS monomers into fibrils in a co- operative and nucleation-dependent manner. The accumulation of αS in the brain has been linked to the development of Parkinson's disease (PD). Amino terminally acetylated αS (Ac-αS) is the physiologically relevant form of the protein in humans. The crowded pre-synaptic milieu is home to several charged metabolites that can reach concentrations at the molar scale in vivo and display remarkable protein-stabilizing prop- erties. High concentrations of charged metabolites are a vital prerequisite for the formation of biocompatible ionic liquids (ILs), hinting at the possibility of the formation of endogenous ILs. The aim of the current study was to assess the effect of a putative naturally occurring IL, choline glutamate ([Ch][Glu]), on the stability of Ac-αS. Fibrillation assays identified [Ch][Glu] and NaCl as destabilizing ionic compounds that interact with αS variants in a concentration- dependent fashion. Nuclear magnetic resonance spectroscopy (NMR) revealed an unexpected contrasting behavior of acetylated and non-acetylated αS when interacting with [Ch][Glu]. These differ- ences are consistent with a more effective destabilization of Ac-αS which might be related to a of the early onset disruption of N-terminal long-range stabilizing interactions. This relatively straightforward in vitro model can be used to elucidate on protein stability and hence fibrillation propensity as a function of osmolyte fluctuations. |
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| Autores principais: | Brigham, Fredi Jovani Soares |
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| Assunto: | Parkinson's Disease Acetylated Alpha-Synuclein Ionic Liquids Choline Glutamate |
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| Ano: | 2023 |
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| País: | Portugal |
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| Tipo de documento: | dissertação de mestrado |
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| Tipo de acesso: | acesso aberto |
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| Instituição associada: | Universidade Nova de Lisboa |
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| Idioma: | inglês |
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| Origem: | Repositório Institucional da UNL |
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