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Brain Transcriptome Analysis Links Deficiencies of Stress-Responsive Proteins to the Pathomechanism of Kii ALS/PDC
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 br...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278732/ https://www.ncbi.nlm.nih.gov/pubmed/32422904 http://dx.doi.org/10.3390/antiox9050423 |
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author | Morimoto, Satoru Ishikawa, Mitsuru Watanabe, Hirotaka Isoda, Miho Takao, Masaki Nakamura, Shiho Ozawa, Fumiko Hirokawa, Yoshifumi Kuzuhara, Shigeki Okano, Hideyuki Kokubo, Yasumasa |
author_facet | Morimoto, Satoru Ishikawa, Mitsuru Watanabe, Hirotaka Isoda, Miho Takao, Masaki Nakamura, Shiho Ozawa, Fumiko Hirokawa, Yoshifumi Kuzuhara, Shigeki Okano, Hideyuki Kokubo, Yasumasa |
author_sort | Morimoto, Satoru |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7278732 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72787322020-06-12 Brain Transcriptome Analysis Links Deficiencies of Stress-Responsive Proteins to the Pathomechanism of Kii ALS/PDC Morimoto, Satoru Ishikawa, Mitsuru Watanabe, Hirotaka Isoda, Miho Takao, Masaki Nakamura, Shiho Ozawa, Fumiko Hirokawa, Yoshifumi Kuzuhara, Shigeki Okano, Hideyuki Kokubo, Yasumasa Antioxidants (Basel) Article 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. MDPI 2020-05-14 /pmc/articles/PMC7278732/ /pubmed/32422904 http://dx.doi.org/10.3390/antiox9050423 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Morimoto, Satoru Ishikawa, Mitsuru Watanabe, Hirotaka Isoda, Miho Takao, Masaki Nakamura, Shiho Ozawa, Fumiko Hirokawa, Yoshifumi Kuzuhara, Shigeki Okano, Hideyuki Kokubo, Yasumasa Brain Transcriptome Analysis Links Deficiencies of Stress-Responsive Proteins to the Pathomechanism of Kii ALS/PDC |
title | Brain Transcriptome Analysis Links Deficiencies of Stress-Responsive Proteins to the Pathomechanism of Kii ALS/PDC |
title_full | Brain Transcriptome Analysis Links Deficiencies of Stress-Responsive Proteins to the Pathomechanism of Kii ALS/PDC |
title_fullStr | Brain Transcriptome Analysis Links Deficiencies of Stress-Responsive Proteins to the Pathomechanism of Kii ALS/PDC |
title_full_unstemmed | Brain Transcriptome Analysis Links Deficiencies of Stress-Responsive Proteins to the Pathomechanism of Kii ALS/PDC |
title_short | Brain Transcriptome Analysis Links Deficiencies of Stress-Responsive Proteins to the Pathomechanism of Kii ALS/PDC |
title_sort | brain transcriptome analysis links deficiencies of stress-responsive proteins to the pathomechanism of kii als/pdc |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278732/ https://www.ncbi.nlm.nih.gov/pubmed/32422904 http://dx.doi.org/10.3390/antiox9050423 |
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