Effects of different isoforms of apoE on aggregation of the alpha?synuclein protein implicated in Parkinson?s disease

Fatemeh Nouri Emamzadeh, Harmesh Aojula, Patrick C McHugh, David Allsopp

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 alpha-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 alpha-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 alpha-synuclein is influenced by apoE concentration. At low concentrations of apoE (15 nM) of these isoforms, where a decrease in the aggregation of alpha-synuclein was noted. The data show that exceptionally low levels of apoE may seed alpha-syn aggregation, which could potentially lead to the pathogenesis of alpha?synuclein-induced neurodegeneration. On the other hand, higher levels of apoE could potentially lower the degree of alpha-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.
Original languageEnglish
Pages (from-to)146-151
Number of pages6
JournalNeuroscience Letters
Volume618
Early online date24 Feb 2016
DOIs
Publication statusPublished - 8 Apr 2016

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Synucleins
alpha-Synuclein
Apolipoproteins E
Protein Isoforms
Apolipoprotein E4
Proteins
Apolipoprotein E2
Apolipoprotein E3
Lewy Bodies
Dopaminergic Neurons
Brain Diseases
Substantia Nigra
Age of Onset
Immunoassay
Seeds

Cite this

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title = "Effects of different isoforms of apoE on aggregation of the alpha?synuclein protein implicated in Parkinson?s disease",
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 alpha-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 alpha-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 alpha-synuclein is influenced by apoE concentration. At low concentrations of apoE (15 nM) of these isoforms, where a decrease in the aggregation of alpha-synuclein was noted. The data show that exceptionally low levels of apoE may seed alpha-syn aggregation, which could potentially lead to the pathogenesis of alpha?synuclein-induced neurodegeneration. On the other hand, higher levels of apoE could potentially lower the degree of alpha-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.",
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Effects of different isoforms of apoE on aggregation of the alpha?synuclein protein implicated in Parkinson?s disease. / Emamzadeh, Fatemeh Nouri; Aojula, Harmesh; McHugh, Patrick C; Allsopp, David.

In: Neuroscience Letters, Vol. 618, 08.04.2016, p. 146-151.

Research output: Contribution to journalArticle

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AU - Allsopp, David

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AB - 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 alpha-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 alpha-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 alpha-synuclein is influenced by apoE concentration. At low concentrations of apoE (15 nM) of these isoforms, where a decrease in the aggregation of alpha-synuclein was noted. The data show that exceptionally low levels of apoE may seed alpha-syn aggregation, which could potentially lead to the pathogenesis of alpha?synuclein-induced neurodegeneration. On the other hand, higher levels of apoE could potentially lower the degree of alpha-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.

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