Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Morimoto, Satoru, Ishikawa, Mitsuru, Watanabe, Hirotaka, Isoda, Miho, Takao, Masaki, Nakamura, Shiho, Ozawa, Fumiko, Hirokawa, Yoshifumi, Kuzuhara, Shigeki, Okano, Hideyuki, Kokubo, Yasumasa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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
_version_ 1783543399493664768
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
work_keys_str_mv AT morimotosatoru braintranscriptomeanalysislinksdeficienciesofstressresponsiveproteinstothepathomechanismofkiialspdc
AT ishikawamitsuru braintranscriptomeanalysislinksdeficienciesofstressresponsiveproteinstothepathomechanismofkiialspdc
AT watanabehirotaka braintranscriptomeanalysislinksdeficienciesofstressresponsiveproteinstothepathomechanismofkiialspdc
AT isodamiho braintranscriptomeanalysislinksdeficienciesofstressresponsiveproteinstothepathomechanismofkiialspdc
AT takaomasaki braintranscriptomeanalysislinksdeficienciesofstressresponsiveproteinstothepathomechanismofkiialspdc
AT nakamurashiho braintranscriptomeanalysislinksdeficienciesofstressresponsiveproteinstothepathomechanismofkiialspdc
AT ozawafumiko braintranscriptomeanalysislinksdeficienciesofstressresponsiveproteinstothepathomechanismofkiialspdc
AT hirokawayoshifumi braintranscriptomeanalysislinksdeficienciesofstressresponsiveproteinstothepathomechanismofkiialspdc
AT kuzuharashigeki braintranscriptomeanalysislinksdeficienciesofstressresponsiveproteinstothepathomechanismofkiialspdc
AT okanohideyuki braintranscriptomeanalysislinksdeficienciesofstressresponsiveproteinstothepathomechanismofkiialspdc
AT kokuboyasumasa braintranscriptomeanalysislinksdeficienciesofstressresponsiveproteinstothepathomechanismofkiialspdc