Targeting Tyro3 ameliorates a model of PGRN-mutant FTLD-TDP via tau-mediated synaptic pathology

Kyota Fujita; Xigui Chen; Hidenori Homma; Kazuhiko Tagawa; Mutsuki Amano; Ayumu Saito; Seiya Imoto; Hiroyasu Akatsu; Yoshio Hashizume; Kozo Kaibuchi; Satoru Miyano; Hitoshi Okazawa

doi:10.1038/s41467-018-02821-z

Nature Communications (Jan 2018)

Targeting Tyro3 ameliorates a model of PGRN-mutant FTLD-TDP via tau-mediated synaptic pathology

Kyota Fujita,
Xigui Chen,
Hidenori Homma,
Kazuhiko Tagawa,
Mutsuki Amano,
Ayumu Saito,
Seiya Imoto,
Hiroyasu Akatsu,
Yoshio Hashizume,
Kozo Kaibuchi,
Satoru Miyano,
Hitoshi Okazawa

Affiliations

Kyota Fujita: Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University
Xigui Chen: Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University
Hidenori Homma: Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University
Kazuhiko Tagawa: Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University
Mutsuki Amano: Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University
Ayumu Saito: Human Genome Center, Institute of Medical Science, The University of Tokyo
Seiya Imoto: Health Intelligence Center, Institute of Medical Science, The University of Tokyo
Hiroyasu Akatsu: Department of Medicine for Aging in Place and Community-Based Medical Education, Nagoya City University Graduate School of Medical Sciences
Yoshio Hashizume: Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University
Kozo Kaibuchi: Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University
Satoru Miyano: Human Genome Center, Institute of Medical Science, The University of Tokyo
Hitoshi Okazawa: Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University

DOI: https://doi.org/10.1038/s41467-018-02821-z
Journal volume & issue: Vol. 9, no. 1
pp. 1 – 21

Abstract

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Progranulin (PGRN) mutations cause frontotemporal lobe dementia with TDP-43 pathology. Here the authors develop a mutant PGRN knock-in mouse model of the disease, and show that Tyro3, a tyrosine kinase membrane receptor that acts upstream of PKC and MAPK, is inhibited by PGRN which contributes to pathology in this model.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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