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.
Bibliographical noteFunding Information:
Inkyung Jung was supported by National Research Foundation of Korea [ 2020R1A2C400146413 and 2022R1A5A1026413 ].
Professor Kee K. Kim was supported by National Research Foundation of Korea [ 2022R1A2C1003870 and 2020R1A2C4001652 ].
Sun-Shin Cha was supported by Ministry of Oceans and Fisheries , Korea [ 20170305 ].
© 2023 The Authors
- Alternative splicing
- Parkinson's disease