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A novel splicing variant of DJ-1 in Parkinson's disease induces mitochondrial dysfunction

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-matche...

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Detalles Bibliográficos
Autores principales: Cho, Namjoon, Joo, Jaegeon, Choi, Sunkyung, Kang, Bu-Gyeong, Lee, Andrew J., Youn, So-Yeon, Park, Su-Hyung, Kim, Eun-Mi, Masliah, Eliezer, Ko, Yuji, Cha, Sun-Shin, Jung, Inkyung, Kim, Kee K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10006478/
https://www.ncbi.nlm.nih.gov/pubmed/36915530
http://dx.doi.org/10.1016/j.heliyon.2023.e14039
Descripción
Sumario: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-1(ΔE6)), 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.