Research Project
Grant-in-Aid for Challenging Exploratory Research
TAR DNA-binding protein 43 kDa (TDP-43) encoded by TARDBP gene is an RNA-binding protein, the nuclear depletion of which is the histopathological hallmark of amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder affecting both upper and lower motor neurons. Besides motor symptoms, ALS patients often develop non-neuronal signs including glucose intolerance, but underlying pathomechanism is still controversial: impaired insulin secretion and/or insulin resistance. Here we show that ALS subjects have reduced early phase insulin secretion and that nuclear localization TDP-43 is lost in the islets of autopsied pancreas of ALS. Loss of TDP-43 inhibits early phase insulin secretion in both Min6 cells and pancreatic beta cell-specific Tardbp knock-out mice. Nuclear loss of TDP-43 is thus implicated in not only selective loss of motor neurons, but glucose intolerance due to impaired insulin secretion at an early stage of ALS.
All 2017 2016
All Journal Article (3 results) (of which Int'l Joint Research: 1 results, Peer Reviewed: 3 results, Open Access: 2 results, Acknowledgement Compliant: 1 results) Presentation (4 results) (of which Int'l Joint Research: 2 results, Invited: 1 results)
Cell Reports
Volume: 18 Issue: 5 Pages: 1118-1131
10.1016/j.celrep.2017.01.013
PLoS One.
Volume: 11(12) Issue: 12 Pages: e0168846-e0168846
10.1371/journal.pone.0168846
Brain
Volume: 139 Issue: 12 Pages: 3187-3201
10.1093/brain/aww237
