TAR DNA-Binding Protein 43 and Disrupted in Schizophrenia 1 Coaggregation Disrupts Dendritic Local Translation and Mental Function in Frontotemporal Lobar Degeneration

Biological Psychiatry
Ryo EndoMotomasa Tanaka

Abstract

Neurodegenerative diseases involving protein aggregation often accompany psychiatric symptoms. Frontotemporal lobar degeneration (FTLD) associated with TAR DNA-binding protein 43 (TDP-43) aggregation is characterized by progressive neuronal atrophy in frontal and temporal lobes of cerebral cortex. Furthermore, patients with FTLD display mental dysfunction in multiple behavioral dimensions. Nevertheless, their molecular origin for psychiatric symptoms remains unclear. In FTLD neurons and mouse models with TDP-43 aggregates, we examined coaggregation between TDP-43 and disrupted in schizophrenia 1 (DISC1), a key player in the pathology of mental conditions and its effects on local translation in dendrites and psychiatric behaviors. The protein coaggregation and the expression level of synaptic proteins were also investigated with postmortem brains from patients with FTLD (n = 6). We found cytosolic TDP-43/DISC1 coaggregates in brains of both FTLD mouse model and patients with FTLD. At the mechanistic levels, the TDP-43/DISC1 coaggregates disrupted the activity-dependent dendritic local translation through impairment of translation initiation and, in turn, reduced synaptic protein expression. Behavioral deficits detected in FTLD m...Continue Reading

References

Apr 26, 2003·Science·Benoit I GiassonVirginia M-Y Lee
Oct 23, 2003·Human Molecular Genetics·Stephanie CemanStephen T Warren
Aug 20, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Giovanni StefaniRobert B Darnell
Jan 5, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Shinichiro TayaKozo Kaibuchi
Apr 10, 2007·Annual Review of Neuroscience·Harry T Orr, Huda Y Zoghbi
May 8, 2007·Neuron·Steven J ClapcoteJohn C Roder
Aug 7, 2007·Proceedings of the National Academy of Sciences of the United States of America·Takatoshi HikidaAkira Sawa
Sep 13, 2007·Nature Reviews. Neuroscience·Clive R Bramham, David G Wells
Dec 20, 2007·Journal of Neurochemistry·I-Fan WangC-K James Shen
Apr 11, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·S Rutger LeliveldCarsten Korth
Oct 17, 2008·Nature·Melissa B Ramocki, Huda Y Zoghbi
Mar 24, 2009·Nature Methods·Enrico K SchmidtPhilippe Pierre
Feb 9, 2010·Nature Neuroscience·Akiko Hayashi-TakagiAkira Sawa
Apr 14, 2010·Proceedings of the National Academy of Sciences of the United States of America·Julie GauthierUNKNOWN S2D Team
May 27, 2011·Acta Neuropathologica·Keith A JosephsDennis W Dickson
Jul 26, 2011·Trends in Molecular Medicine·Todd J CohenJohn Q Trojanowski
Sep 1, 2011·The EMBO Journal·Michael Doyle, Michael A Kiebler
Oct 22, 2011·Trends in Molecular Medicine·David J PorteousAkira Sawa
Nov 4, 2011·Proceedings of the National Academy of Sciences of the United States of America·Mirna KvajoJoseph A Gogos
Nov 11, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Liqun Liu-YesucevitzBenjamin Wolozin
Nov 19, 2011·Nature Reviews. Neuroscience·Nicholas J Brandon, Akira Sawa
Dec 1, 2011·Nature Reviews. Neuroscience·Edward B LeeJohn Q Trojanowski
Feb 15, 2012·Nature Reviews. Neurology·Muireann IrishJohn R Hodges
Mar 20, 2012·Cell·Yadong Huang, Lennart Mucke
Jan 18, 2013·Nature·Daniel H Ebert, Michael E Greenberg
Apr 16, 2013·Neuron·Yong-Hui Jiang, Michael D Ehlers
Aug 13, 2013·Neuron·Shuo-Chien LingDon W Cleveland
Nov 22, 2013·Biochemical Society Transactions·Marco BaralleFrancisco E Baralle
Jan 28, 2014·Nature·Menachem FromerMichael C O'Donovan
Jan 28, 2014·Nature·Shaun M PurcellPamela Sklar
Jul 18, 2014·Annual Review of Neuroscience·Shelly A BuffingtonMauro Costa-Mattioli
Aug 22, 2014·Human Molecular Genetics·David BlumTiago F Outeiro
Sep 17, 2014·Molecular Psychiatry·N ShahaniA Sawa
Oct 8, 2014·ASN Neuro·Reddy Ranjith Kumar SamaDaryl A Bosco
Nov 8, 2014·Human Molecular Genetics·Hiroaki SuzukiMasaaki Matsuoka
Nov 28, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Alyssa N CoyneDaniela C Zarnescu

❮ Previous
Next ❯

Citations

Dec 24, 2018·Neuropathology and Applied Neurobiology·B BorroniE Buratti
Jun 6, 2020·Cellular and Molecular Life Sciences : CMLS·Vivek M Advani, Pavel Ivanov
Feb 6, 2020·Frontiers in Molecular Biosciences·Maximilian Paul Thelen, Min Jeong Kye
Dec 29, 2020·Frontiers in Cellular Neuroscience·Santiago E CharifLionel M Igaz
Sep 23, 2019·Biological Psychiatry·Toshifumi TomodaAkira Sawa
Mar 2, 2021·Neural Regeneration Research·Jin-Xin LuGang Chen
Jul 20, 2021·Frontiers in Integrative Neuroscience·María GamarraJimena Baleriola

❮ Previous
Next ❯

Related Concepts

Related Feeds

Attention Disorders

Attention is involved in all cognitive activities, and attention disorders are reported in patients with various neurological diseases. Here are the latest discoveries pertaining to attention disorders.