Role Identified for Neuronal Protein in Dementia of Frontotemporal Lobar Degeneration Interview with:
Shinsuke Ishigaki

Department of Neurology
Department of Therapeutics for Intractable Neurological Disorders
Nagoya University Graduate School of Medicine
Nagoya,Japan What is the background for this study? What are the main findings?

Response: Frontotemporal lobar degeneration (FTLD) is a pathological process that
has been characterized by personality changes, abnormal behaviors,
language impairment, and progressive dementia. The genetic and
pathological similarities in fused in sarcoma (FUS), transactive
response (TAR) DNA-binding protein 43 (TDP-43), and C9orf72 in relation
to FTLD and amyotrophic lateral sclerosis (ALS) have recently lead to
the recognition that the two conditions represent points on a spectrum
of a single disease entity. Additionally, Frontotemporal lobar degeneration has also been classified as a tauopathy, characterized by an accumulation of phosphorylated
microtubule-associated protein tau (tau) in affected neurons.

Our study demonstrated a biological link between FUS/SFPQ and the regulation of
tau isoforms involved in the early phase of Frontotemporal lobar degeneration. What should readers take away from your report?

Response: It has been recognized that FTLD-tau and FTLD-MND as separated disease
entities. In this manuscript we proposed a novel link between FUS/SFPQ
and tau isoforms that implies underlying mechanism in the early disease
phase in a certain spectrum of both FTLD-tau and FTLD-MND. Thus, the FUS
and SFPQ-silenced mice that we generated are expected to be useful
disease models for the development of therapeutics for Frontotemporal lobar degeneration. What recommendations do you have for future research as a result of this study?

Response: We will investigate the levels of FUS and SFPQ interactions in
postmortem brain tissues from various neurodegenerative diseases
including FTLD, PSP, CBD and AD. This can allow us to see whether a loss
of FUS/SFPQ functionality leading to tau isoform disequilibrium is the
basis for the mechanism underlying 4R-tau dominant tauopathies. Thank you for your contribution to the community.

Altered Tau Isoform Ratio Caused by Loss of FUS and SFPQ Function Leads to FTLD-like Phenotypes
Shinsuke Ishigaki12, Correspondence information about the author Shinsuke Ishigaki Email the author Shinsuke Ishigaki,Yusuke Fujioka,,Yohei Okada,Yuichi Riku,Tsuyoshi Udagawa,Daiyu Honda,Satoshi Yokoi,Kuniyuki Endo,Kensuke Ikenaka,Shinnosuke Takagi,Yohei Iguchi,Naruhiko Sahara,Akihiko Takashima,Hideyuki Okano,Mari Yoshida,Hitoshi Warita,Masashi Aoki,Hirohisa Watanabe,Haruo Okado,Masahisa Katsuno, Gen Sobue13, Correspondence information about the author Gen Sobue
Cell Reports

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Last Updated on February 17, 2017 by Marie Benz MD FAAD