The importance of different genetic backgrounds in α-synuclein pathology studies in C. elegans

Yiru A. Wang, M.G. Sterken, Y. Nie, S. Harvey, J.E. Kammenga

Research output: Contribution to conferenceAbstractAcademic

Abstract

The α-synuclein, encoded by the SNCA gene, plays a key role in progressive degeneration in the human nervous system, such as its associated Parkinson’s diseases (PD) and Dementia with Lewy bodies (DLB). Progressively increasing oligomeric complexes of α-synuclein with advancing age mediate disruption of cellular homeostasis, resulting in neuronal death. However, polymorphic regulatory elements in different genetic backgrounds can affect this complex pathologic mechanism. The nematode Caenorhabditis elegans is a valuable model species in which to study α-synuclein associated molecular mechanism because of its high level of gene function conservation compared to humans. So far research focused on α-synuclein associated pathological mechanisms in C. elegans mutants in a single worm genotype, the canonical N2 strain. This limits the ability to explore how naturally varying alleles alter the pathogenicity. Therefore, we introduced the human copy of α-synuclein (unc-54::α-Syn::YFP) from a transgenic N2-model into other five divergent C. elegans strains. By quantifying both α-synuclein gene expression and protein accumulation levels in these worms with different genetic backgrounds, we found the genetic background variably influenced on α-synuclein accumulation. Variable lipid contents and body-length changes were measured among the wild-type and transgenic worms, which suggests that genotypic-phenotypic response to α-synuclein could be affected by natural variation. There are also other phenotypic variation related to the α-synuclein aggregation and toxicity identified in previous study, e.g. its induced genome-wide transcriptional variation. Taken together, we suggest that the employment of variable genetic backgrounds into studies of proteopathic disorder with nematode C. elegans can offer an important insight to understand individual genetic differences regarding misfolded proteins aggregates and their cytotoxic effects.
Original languageEnglish
Publication statusPublished - 28 Nov 2019
EventZoology 2019 - GELIFES, Groningen, Netherlands
Duration: 27 Nov 201929 Nov 2019

Conference

ConferenceZoology 2019
CountryNetherlands
CityGroningen
Period27/11/1929/11/19

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Wang, Y. A., Sterken, M. G., Nie, Y., Harvey, S., & Kammenga, J. E. (2019). The importance of different genetic backgrounds in α-synuclein pathology studies in C. elegans. Abstract from Zoology 2019, Groningen, Netherlands.