Effects of different isoforms of apoE on aggregation of the α‐synuclein protein implicated in Parkinson's disease. (8th April 2016)

• Record Type: Journal Article
• Authors: Emamzadeh, Fatemeh Nouri; Aojula, Harmesh; McHugh, Patrick C.; Allsop, David
• Is Part Of: Neuroscience letters. Volume 618(2016)
• Page Start: 146
• Page End: 151
• Publication Date: 2016-04-08
• Subjects: PD Parkinson's disease -- Aβ β-amyloid -- CSF cerebrospinal fluid -- R-α-syn recombinant α-synuclein -- ThT thioflavin T -- TRF time-resolved fluorescence -- LBs Lewy bodies -- SN substantia nigra; Parkinson's disease -- Lewy body -- α-Synuclein -- Apolipoprotein E -- Aggregation; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2016.02.042
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: ThT assay demonstrates aggregation of α-synuclein is influenced by apolipoprotein E. Sandwich ELISA indicates the observed α-synuclein aggregates were multimeric in nature. Low levels of apoE stimulate α-synuclein aggregation while higher level supresses. Among the different isoforms tested apoE4 has the greatest stimulatory effect. Apolipoproteins may have a role in pathogenesis of Parkinson's disease by influencing the aggregation of α-synuclein. Abstract: Parkinson's disease is a progressive brain disorder due to the degeneration of dopaminergic neurons in the substantia nigra. 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.