Differential interaction between iron and mutant alpha-synuclein causes distinctive Parkinsonian phenotypes in Drosophila
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摘要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 that express A53T and A30P mutant alpha-synuclein. We provided the first in vivo evidence that iron overload could induce distinctive neuropathology and disease phenotypes in mutant but not WT alpha-synuclein expressing flies, providing insights to the cause of clinical features selectively exhibited by mutant alpha-synuclein carriers. (C) 2016 Elsevier B.V. All rights reserved.
著者Zhu ZJ, Wu KC, Yung WH, Qian ZM, Ke Y
期刊名稱BBA - Molecular Basis of Disease
出版年份2016
月份4
日期1
卷號1862
期次4
出版社ELSEVIER SCIENCE BV
頁次518 - 525
國際標準期刊號0925-4439
電子國際標準期刊號0006-3002
語言英式英語
關鍵詞A53T and A30P; Alpha-synuclein; Dopaminergic neuron; Drosophila melanogaster; Iron; Parkinson's disease
Web of Science 學科類別Biochemistry & Molecular Biology; Biophysics; Cell Biology

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