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Identifier |
000423779 |
Title |
Investigating the role of lipid metabolism in α- synuclein aggregation and toxicity in a Caenorhabditis elegans model of Parkinson’s disease |
Alternative Title |
Ερευνώντας το ρόλο του λιπιδιακού μεταβολισμού στην συσσωμάτωση α-συνουκλεϊνική και τοξικότητα χρησιμοποιώντας τον Caenorhabditis elegans ως μοντέλο της ασθένειας Πάρκισον. |
Author
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Χανιωτάκης, Εμμανουήλ Ν.
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Thesis advisor
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Γανωτάκης, Δημήτριος
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Abstract |
Lipid metabolism plays a critical role in α-synuclein aggregation; a-synuclein is a
protein whose role is critical in Parkinson’s disease (PD) progression. Environmental
and genetic factors can accelerate the progression of PD. Interestingly, interaction
between lipids and α-synuclein can affect α-synuclein aggregation. The mechanism
and outcome of the lipid interaction with α-synuclein is still very contradicted. This
study aims to provide insight into the role of fatty acids (FA) metabolism on α-
synuclein aggregation. The nematode Caenorhabditis elegans was used as a model
organism to examine the effect of specific enzymes that are involved in fatty acid
metabolism. We took advantage of an established C. elegans PD model that
overexpresses human α-synuclein fused with a green fluorescent protein (GFP) in
order to study protein aggregation and its effects on C. elegan’s health. We observed
that silencing of the Δ-9 desaturase genes fat-6 and fat-7 results in a reduction of α-
synuclein aggregation and an improvement in healthspan. On the contrary, silencing
of a Δ-12 and a Δ-3 desaturase encoding genes, namely fat-2 and fat-3 respectively,
which act downstream of FAT-6 and FAT-7 enzymes increased aggregation and
toxicity. Moreover, the role of autophagy was also investigated, as it is known that
autophagy aids in degradation of protein aggregates and that loss of autophagic
proteins can lead to neurodegeneration in the central nervous system[1, 2]. We found
that the effect of fat-6 knockdown on α-synuclein aggregation is, at least partly,
independent of autophagy.
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Language |
English |
Subject |
C. elegans |
Issue date |
2019-07-24 |
Collection
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School/Department--School of Sciences and Engineering--Department of Chemistry--Post-graduate theses
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Type of Work--Post-graduate theses
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Permanent Link |
https://elocus.lib.uoc.gr//dlib/d/4/b/metadata-dlib-1563270191-569958-27716.tkl
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Views |
459 |