Differential interaction between iron and mutant alpha-synuclein causes distinctive Parkinsonian phenotypes in Drosophila

Biochimica Et Biophysica Acta
Zhou-Jing ZhuYa Ke

Abstract

Alpha-synuclein aggregation is the central hallmark of both sporadic and familial Parkinson's disease (PD). Patients with different PD-causing genetic defects of alpha-synuclein usually show distinctive clinical features that are atypical to sporadic PD. Iron accumulation is invariably found in PD. Recent studies showed that mutant and wild-type alpha-synuclein may have differential interaction with iron and mutant alpha-synuclein toxicity could be preferentially exacerbated by iron. We hence hypothesized that iron overload could selectively influence mutant alpha-synuclein toxicity and disease phenotypes. To test the hypothesis, we investigated if Drosophila melanogaster over-expressing A53T, A30P, and wild-type (WT) alpha-synuclein have different responses to iron treatment. We showed that iron treatment induced similar reduction of survival rate in all flies but induced a more severe motor decline in A53T and A30P mutant alpha-synuclein expressing flies, suggesting interaction between mutant alpha-synuclein and iron. Although no significant difference in total head iron content was found among these flies, we demonstrated that iron treatment induced selective DA neuron loss in motor-related PPM3 cluster only in the flies tha...Continue Reading

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Citations

Apr 4, 2016·Molecular Neurobiology·Hong JiangJunxia Xie
May 20, 2016·BMC Neuroscience·P Githure M'Angale, Brian E Staveley
Sep 28, 2016·PeerJ·P Githure M'Angale, Brian E Staveley
Jan 10, 2018·Frontiers in Genetics·Juan A Navarro, Stephan Schneuwly
Jun 14, 2017·BMC Research Notes·P Githure M'Angale, Brian E Staveley
Jul 8, 2017·International Journal of Molecular Sciences·Pablo Calap-QuintanaMaría Dolores Moltó
Jun 15, 2018·BMC Developmental Biology·Melanie MorrisNorma Andrea Velazquez-Ulloa
Feb 7, 2019·Frontiers in Neuroscience·Karina JoppePaul Lingor
Nov 7, 2019·Oxidative Medicine and Cellular Longevity·Dinendra L Abeyawardhane, Heather R Lucas
Jun 8, 2017·Frontiers in Physiology·Yu-Fu ZhouYa Ke
Aug 24, 2019·Frontiers in Neurology·Franziska HopfnerUNKNOWN Fair-Park II study group

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