論文

査読有り 国際誌
2020年5月14日

Brain Transcriptome Analysis Links Deficiencies of Stress-Responsive Proteins to the Pathomechanism of Kii ALS/PDC.

Antioxidants (Basel, Switzerland)
  • Satoru Morimoto
  • ,
  • Mitsuru Ishikawa
  • ,
  • Hirotaka Watanabe
  • ,
  • Miho Isoda
  • ,
  • Masaki Takao
  • ,
  • Shiho Nakamura
  • ,
  • Fumiko Ozawa
  • ,
  • Yoshifumi Hirokawa
  • ,
  • Shigeki Kuzuhara
  • ,
  • Hideyuki Okano
  • ,
  • Yasumasa Kokubo

9
5
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3390/antiox9050423

Amyotrophic lateral sclerosis and Parkinsonism-dementia complex (ALS/PDC) is a unique endemic neurodegenerative disease, with high-incidence foci in Kii Peninsula, Japan. To gather new insights into the pathological mechanisms underlying Kii ALS/PDC, we performed transcriptome analyses of patient brains. We prepared frozen brains from three individuals without neurodegenerative diseases, three patients with Alzheimer's disease, and 21 patients with Kii ALS/PDC, and then acquired microarray data from cerebral gray and white matter tissues. Microarray results revealed that expression levels of genes associated with heat shock proteins, DNA binding/damage, and senescence were significantly altered in patients with ALS/PDC compared with healthy individuals. The RNA expression pattern observed for ALS-type brains was similar to that of PDC-type brains. Additionally, pathway and network analyses indicated that the molecular mechanism underlying ALS/PDC may be associated with oxidative phosphorylation of mitochondria, ribosomes, and the synaptic vesicle cycle; in particular, upstream regulators of these mechanisms may be found in synapses and during synaptic trafficking. Furthermore, phenotypic differences between ALS-type and PDC-type were observed, based on HLA haplotypes. In conclusion, determining the relationship between stress-responsive proteins, synaptic dysfunction, and the pathogenesis of ALS/PDC in the Kii peninsula may provide new understanding of this mysterious disease.

リンク情報
DOI
https://doi.org/10.3390/antiox9050423
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32422904
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278732

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