Effects of different isoforms of apoE on aggregation of the α- synuclein protein implicated in Parkinson's disease

Nouri Emamzadeh, Fatemeh and Aojula, Harmesh and McHugh, Patrick and Allsop, David (2016) Effects of different isoforms of apoE on aggregation of the α- synuclein protein implicated in Parkinson's disease. Neuroscience Letters, 618. pp. 146-151. ISSN 0304-3940

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Abstract

Parkinson's disease is a progressive brain disorder due to the degeneration of dopaminergic neurons in the SN. The accumulation of aggregated forms of α-synuclein protein into Lewy bodies is one of the characteristic features of this disease although the pathological role of any such protein deposits in causing neurodegeneration remains elusive. Here, the effects of different apolipoprotein E isoforms (apoE2, apoE3, apoE4) on the aggregation of α-synuclein in vitro were examined using thioflavin T assays and also an immunoassay to detect the formation of multimeric forms. Our results revealed that the aggregation of α-synuclein is influenced by apoE concentration. At low concentrations of apoE (<15 nM), all of the isoforms were able to increase the aggregation of α-synuclein (50 μM), with apoE4 showing the greatest stimulatory effect. This is in contrast to a higher concentration (>15 nM) of these isoforms, where a decrease in the aggregation of α-synuclein was noted. The data show that exceptionally low levels of apoE may seed α-syn aggregation, which could potentially lead to the pathogenesis of α synuclein-induced neurodegeneration. On the other hand, higher levels of apoE could potentially lower the degree of α-synuclein aggregation and confer protection. The differential effects noted with apoE4 could explain why this particular isoform results in an earlier age of onset for Parkinson's disease.

Item Type:
Journal Article
Journal or Publication Title:
Neuroscience Letters
Additional Information:
This is the author’s version of a work that was accepted for publication in Neuroscience Letters. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Neuroscience Letters, 618, 2016 DOI: 10.1016/j.neulet.2016.02.042
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2800
Subjects:
ID Code:
78444
Deposited By:
Deposited On:
29 Feb 2016 14:50
Refereed?:
Yes
Published?:
Published
Last Modified:
09 Aug 2020 04:03