News Releases & Research Results Discovery of a common mechanism underlying onset of a group of dementias called the frontotemporal lobar degeneration spectrum diseases

The results of the collaborative research project conducted by Designated Associate Professor Shinsuke Ishigaki and Designated Professor Gen Sobue of Nagoya University Graduate School of Medicine, and others.

• The pathological examinations showed that an aberrant intranuclear microlocalization of the RNA-binding proteins, fused-in sarcoma (FUS) and splicing factor, proline- and glutamine-rich (SFPQ) in neurons and the related changes in tau isoform* composition underlie a common pathology of a group of dementias called the frontotemporal lobar degeneration (FTLD) spectrum diseases, which include FTLD, a kind of dementia characterized by personality changes, affective disorder, and speech disorder, and other neural degenerative disorders associated with continued symptoms (such as amyotrophic lateral sclerosis [ALS], progressive supranuclear palsy [PSP], and corticobasal degeneration [CBD]).
  *The product of alternative splicing of the MAPT gene (a gene encoding tau proteins) regulated by the RNA-binding proteins, FUS and SFPQ. It mainly consists of two types called 3-repeat tau (3R-tau) and 4-repeat tau (4R-tau).
• The results of this research project should facilitate the development of therapeutic drugs targeting the qualitative loss of function of FUS and SFPQ and the related changes in tau isoform composition.

This research project was conducted with the support of the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) and the Strategic Research Program for Brain Sciences (SRPBS) by AMED.

The results of this research project were published online in Brain, an international scientific journal, on August 7.

Ishigaki S., et al. Aberrant interaction between FUS and SFPQ in neurons of a wide-range of FTLD spectrum diseases Brain
DOI：10.1093/brain/awaa196