Abstract
Abnormal oligomerisation and aggregation of the protein called alpha-synuclein (α-syn) are the key events in the pathogenesis of Parkinson’s disease (PD). Recent discoveries revealed cellular pathways that potentially relate neurodegenerative disease (ND) to abnormal functioning of mitochondria or anomalous glucose metabolism. In this study we describe for the first time strains of the thermotolerant methylotrophic yeast Hansenula polymorpha that produce human GFP-tagged α-syn as a new model of molecular processes leading to PD. We observed that NCYC495 -SNCA wild-type strain did not form visible α-syn amyloid-like aggregates but exhibited plasma membrane perforations and cytoplasm leakage. gcr 1-2 -SNCA mutant strain deficient in catabolite repression and glucose transport exhibited enhanced aggregation of fluorescently tagged α-syn. However, the observed differences did not result from the impaired glucose metabolism as were observed in both α-syn-producing strains grown on glycerol. Production of α-syn was detrimental for both strains and decreased their growth rate on alternative carbon sources. Our data suggests that H. polymorpha may serve as an informative new yeast model for deciphering molecular mechanisms of PD that regulate amyloid formation and degradation under the influence of various extra- and intracellular factors. Keywords: methylotrophic yeast, α-synuclein, amyloids, neurodegeneration.
Highlights
Human neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, dementia with Lewy bodies, and Huntington’s disease belong to the superfami ly of pathologies known as protein misfolding disorders [27]
It is known that these disorders have some common cellular and molecular mechanisms including protein misfolding and aggregation and formation of inclusion bodies
These aggregates usually consist of fibers containing misfolded proteins with β-sheet conformation, termed amyloid [21]
Summary
Human neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, dementia with Lewy bodies, and Huntington’s disease belong to the superfami ly of pathologies known as protein misfolding disorders [27]. It is known that these disorders have some common cellular and molecular mechanisms including protein misfolding and aggregation and formation of inclusion bodies. These aggregates usually consist of fibers containing misfolded proteins with β-sheet conformation, termed amyloid [21]. In PD there is abnormal accumulation of synuclein in neuronal cell bodies, axons, and synapses [11].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
