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Research ArticleNew Research, Disorders of the Nervous System

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

Kyota Fujita, Hidenori Homma, Kanoh Kondo, Masashi Ikuno, Hodaka Yamakado, Kazuhiko Tagawa, Shigeo Murayama, Ryosuke Takahashi and Hitoshi Okazawa
eNeuro 16 August 2018, 5 (4) ENEURO.0217-18.2018; DOI: https://doi.org/10.1523/ENEURO.0217-18.2018
Kyota Fujita
1Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
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Hidenori Homma
1Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
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Kanoh Kondo
1Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
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Masashi Ikuno
2Department of Neurology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-Cho, Sakyo-Ku, Kyoto, 606-8501, Japan
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  • ORCID record for Masashi Ikuno
Hodaka Yamakado
2Department of Neurology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-Cho, Sakyo-Ku, Kyoto, 606-8501, Japan
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Kazuhiko Tagawa
1Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
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Shigeo Murayama
3Department of Neuropathology, Brain Bank for Aging Research, Tokyo Metropolitan Institute of Gerontology, 35-2, Sakae-Cho, Itabashi-ku, Tokyo 173-0015, Japan
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Ryosuke Takahashi
2Department of Neurology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-Cho, Sakyo-Ku, Kyoto, 606-8501, Japan
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Hitoshi Okazawa
1Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
4Center for Brain Integration Research, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
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Abstract

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.

  • Biomarker
  • degeneration
  • MARCKS
  • neurite
  • phosphorylation

Footnotes

  • We report no conflict of interest.

  • This work was supported by Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) from the Japan Agency for Medical Research and Development (AMED; JP18dm0207013h0005); the Strategic Research Program for Brain Sciences (SRPBS; JP18dm0107057h0002); and a Grant-in-Aid for Scientific Research on Innovative Areas “Foundation of Synapse and Neurocircuit Pathology” (22110001, 22110002) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT; to HO).

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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Ser46-Phosphorylated MARCKS Is a Marker of Neurite Degeneration at the Pre-aggregation Stage in PD/DLB Pathology
Kyota Fujita, Hidenori Homma, Kanoh Kondo, Masashi Ikuno, Hodaka Yamakado, Kazuhiko Tagawa, Shigeo Murayama, Ryosuke Takahashi, Hitoshi Okazawa
eNeuro 16 August 2018, 5 (4) ENEURO.0217-18.2018; DOI: 10.1523/ENEURO.0217-18.2018

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Ser46-Phosphorylated MARCKS Is a Marker of Neurite Degeneration at the Pre-aggregation Stage in PD/DLB Pathology
Kyota Fujita, Hidenori Homma, Kanoh Kondo, Masashi Ikuno, Hodaka Yamakado, Kazuhiko Tagawa, Shigeo Murayama, Ryosuke Takahashi, Hitoshi Okazawa
eNeuro 16 August 2018, 5 (4) ENEURO.0217-18.2018; DOI: 10.1523/ENEURO.0217-18.2018
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Keywords

  • biomarker
  • degeneration
  • MARCKS
  • neurite
  • phosphorylation

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