A novel splicing variant of DJ-1 in Parkinson's disease induces mitochondrial dysfunction
- 주제(키워드) Alternative splicing , DJ-1 , Mitochondria , PARK7 , Parkinson's disease
- 등재 SCIE, SCOPUS
- 발행기관 Elsevier Ltd
- 발행년도 2023
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000204191
- 본문언어 영어
- Published As https://doi.org/10.1016/j.heliyon.2023.e14039
초록/요약
Several studies have identified mutations in neuroprotective genes in a few cases of Parkinson's disease (PD); however, the role of alternative splicing changes in PD remains unelucidated. Based on the transcriptome analysis of substantia nigra (SN) tissues obtained from PD cases and age-matched healthy controls, we identified a novel alternative splicing variant of DJ-1, lacking exon 6 (DJ-1ΔE6), frequently detected in the SN of patients with PD. We found that the exon 6 skipping of DJ-1 induces mitochondrial dysfunction and impaired antioxidant capability. According to an in silico modeling study, the exon 6 skipping of DJ-1 disrupts the structural state suitable for the oxidation of the cysteine 106 residue that is a prerequisite for activating its neuroprotective roles. Our results suggest that change in DJ-1 alternative splicing may contribute to PD progression and provide an insight for studying PD etiology and its potential therapeutic targets. © 2023 The Authors
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