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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	Χανιωτάκης, Εμμανουήλ Ν.
Thesis advisor	Γανωτάκης, Δημήτριος
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.
Language	English
Subject	C. elegans
Issue date	2019-07-24
Collection	School/Department--School of Sciences and Engineering--Department of Chemistry--Post-graduate theses
	Type of Work--Post-graduate theses
Permanent Link	https://elocus.lib.uoc.gr//dlib/d/4/b/metadata-dlib-1563270191-569958-27716.tkl
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