Ser46-Phosphorylated MARCKS Is a Marker of Neurite Degeneration at the Pre-aggregation Stage in PD/DLB Pathology

Phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) reflects neurite degeneration at the early stage of Alzheimer’s disease (AD), before extracellular Aβ aggregates are histologically detectable. Here, we demonstrate that similar changes in MARCKS occur in Parkinson’s disease (...

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Autores principales: Fujita, Kyota, Homma, Hidenori, Kondo, Kanoh, Ikuno, Masashi, Yamakado, Hodaka, Tagawa, Kazuhiko, Murayama, Shigeo, Takahashi, Ryosuke, Okazawa, Hitoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society for Neuroscience 2018
Materias:
New Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140116/
https://www.ncbi.nlm.nih.gov/pubmed/30225354
http://dx.doi.org/10.1523/ENEURO.0217-18.2018
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author Fujita, Kyota
Homma, Hidenori
Kondo, Kanoh
Ikuno, Masashi
Yamakado, Hodaka
Tagawa, Kazuhiko
Murayama, Shigeo
Takahashi, Ryosuke
Okazawa, Hitoshi
author_facet Fujita, Kyota
Homma, Hidenori
Kondo, Kanoh
Ikuno, Masashi
Yamakado, Hodaka
Tagawa, Kazuhiko
Murayama, Shigeo
Takahashi, Ryosuke
Okazawa, Hitoshi
author_sort Fujita, Kyota
collection PubMed
description Phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) reflects neurite degeneration at the early stage of Alzheimer’s disease (AD), before extracellular Aβ aggregates are histologically detectable. Here, we demonstrate that similar changes in MARCKS occur in Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) pathologies in both mouse models and human patients. The increase in the level of pSer46-MARCKS began before α-synuclein aggregate formation, at a time when human α-Syn-BAC-Tg/GBA-hetero-KO mice exhibited no symptoms, and was sustained during aging, consistent with the pattern in human postmortem brains. The results strongly imply a common mechanism of pre-aggregation neurite degeneration in AD and PD/DLB pathologies.
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spelling pubmed-61401162018-09-17 Ser46-Phosphorylated MARCKS Is a Marker of Neurite Degeneration at the Pre-aggregation Stage in PD/DLB Pathology Fujita, Kyota Homma, Hidenori Kondo, Kanoh Ikuno, Masashi Yamakado, Hodaka Tagawa, Kazuhiko Murayama, Shigeo Takahashi, Ryosuke Okazawa, Hitoshi eNeuro New Research Phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) reflects neurite degeneration at the early stage of Alzheimer’s disease (AD), before extracellular Aβ aggregates are histologically detectable. Here, we demonstrate that similar changes in MARCKS occur in Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) pathologies in both mouse models and human patients. The increase in the level of pSer46-MARCKS began before α-synuclein aggregate formation, at a time when human α-Syn-BAC-Tg/GBA-hetero-KO mice exhibited no symptoms, and was sustained during aging, consistent with the pattern in human postmortem brains. The results strongly imply a common mechanism of pre-aggregation neurite degeneration in AD and PD/DLB pathologies. Society for Neuroscience 2018-09-04 /pmc/articles/PMC6140116/ /pubmed/30225354 http://dx.doi.org/10.1523/ENEURO.0217-18.2018 Text en Copyright © 2018 Fujita et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle New Research
Fujita, Kyota
Homma, Hidenori
Kondo, Kanoh
Ikuno, Masashi
Yamakado, Hodaka
Tagawa, Kazuhiko
Murayama, Shigeo
Takahashi, Ryosuke
Okazawa, Hitoshi
Ser46-Phosphorylated MARCKS Is a Marker of Neurite Degeneration at the Pre-aggregation Stage in PD/DLB Pathology
title Ser46-Phosphorylated MARCKS Is a Marker of Neurite Degeneration at the Pre-aggregation Stage in PD/DLB Pathology
title_full Ser46-Phosphorylated MARCKS Is a Marker of Neurite Degeneration at the Pre-aggregation Stage in PD/DLB Pathology
title_fullStr Ser46-Phosphorylated MARCKS Is a Marker of Neurite Degeneration at the Pre-aggregation Stage in PD/DLB Pathology
title_full_unstemmed Ser46-Phosphorylated MARCKS Is a Marker of Neurite Degeneration at the Pre-aggregation Stage in PD/DLB Pathology
title_short Ser46-Phosphorylated MARCKS Is a Marker of Neurite Degeneration at the Pre-aggregation Stage in PD/DLB Pathology
title_sort ser46-phosphorylated marcks is a marker of neurite degeneration at the pre-aggregation stage in pd/dlb pathology
topic New Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140116/
https://www.ncbi.nlm.nih.gov/pubmed/30225354
http://dx.doi.org/10.1523/ENEURO.0217-18.2018
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