TDP-43: A Key Therapeutic Target beyond Amyotrophic Lateral Sclerosis

ACS Chemical Neuroscience
Valle PalomoAna Martinez

Abstract

Accumulation of TDP-43 in the cytoplasm of diseased neurons is the pathological hallmark of frontotemporal dementia-TDP (FTLD-TDP) and amyotrophic lateral sclerosis (ALS), two diseases that lack efficacious medicine to prevent or to stop disease progression. The discovery of mutations in the TARDBP gene (encoding the nuclear protein known as TDP-43) in both FTLD and ALS patients provided evidence for a link between TDP-43 alterations and neurodegeneration. Our understanding of TDP-43 function has advanced profoundly in the past several years; however, its complete role and the molecular mechanisms that lead to disease are not fully understood. Here we summarize the recent studies of this protein, its relation to neurodegenerative diseases, and the therapeutic strategies for restoring its homeostasis with small molecules. Finally, we briefly discuss the available cellular and animal models that help to shed light on TDP-43 pathology and could serve as tools for the discovery of pharmacological agents for the treatment of TDP-43-related diseases.

References

Jul 1, 1992·Developmental Dynamics : an Official Publication of the American Association of Anatomists·N R CashmanJ P Antel
May 5, 2000·Journal of Neurology·V SilaniG Scarlato
Aug 15, 2000·Journal of Structural Biology·J D Sipe, A S Cohen
Feb 24, 2001·Annals of the New York Academy of Sciences·M G Spillantini, M Goedert
Oct 10, 2002·Annals of Medicine·Martin Ingelsson, Bradley T Hyman
Mar 1, 2008·Science·Jemeen SreedharanChristopher E Shaw
Sep 19, 2008·Bioorganic & Medicinal Chemistry Letters·Giorgio CozzaStefano Moro
Oct 30, 2008·Journal of Cell Science·Youhna M AyalaFrancisco E Baralle
Nov 20, 2008·Journal of Neuropathology and Experimental Neurology·Claudia SchwabPatrick L McGeer
Jan 1, 2009·Journal of Medicinal Chemistry·Maria MenichincheriErmes Vanotti
Mar 17, 2009·Biochemical and Biophysical Research Communications·Fuyuki KametaniMasato Hasegawa
May 23, 2009·Journal of Cell Science·Brinda RavikumarDavid C Rubinsztein
Jun 27, 2009·Science·Marco SardielloAndrea Ballabio
Aug 5, 2009·The Journal of Biological Chemistry·Antonella CaccamoSalvatore Oddo
Oct 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Iga WegorzewskaRobert H Baloh
Jan 15, 2010·Journal of Cellular and Molecular Medicine·Kurt A Jellinger
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Hans WilsSamir Kumar-Singh
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yan LiJane Y Wu
Mar 4, 2010·Neuro-degenerative Diseases·Jean-Baptiste ChansonMichèle Kiesmann
Jun 10, 2010·Human Molecular Genetics·Peter E A AshChristopher D Link
Jul 14, 2010·Proceedings of the National Academy of Sciences of the United States of America·Shuo-Chien LingDon W Cleveland
Aug 13, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ya-Fei XuLeonard Petrucelli
Sep 11, 2010·Nature·Byung-Hoon LeeDaniel Finley
Nov 11, 2010·Journal of Neurochemistry·Owen A BradyFenghua Hu
Dec 3, 2010·Neuro-degenerative Diseases·Iga Wegorzewska, Robert H Baloh
Dec 7, 2010·The EMBO Journal·Youhna M AyalaFrancisco E Baralle
Dec 30, 2010·Autophagy·Terje Johansen, Trond Lamark
Mar 2, 2011·Nature Neuroscience·Magdalini PolymenidouDon W Cleveland
Oct 28, 2011·Molecular Neurodegeneration·Ya-Fei XuLeonard Petrucelli
Nov 5, 2011·The Journal of Biological Chemistry·Jayarama Krishnan BoseC-K James Shen
Feb 11, 2012·Proceedings of the National Academy of Sciences of the United States of America·Yukio Kawahara, Ai Mieda-Sato

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Citations

Aug 2, 2020·British Journal of Pharmacology·Valle PalomoAna Martinez
Jul 17, 2021·Journal of the Neurological Sciences·Eirini CharonitiChristos Kroupis
Aug 28, 2021·International Journal of Molecular Sciences·Loreto Martínez-GonzálezAna Martínez
Jan 23, 2022·Clinical and Translational Medicine·Georgios PampalakisGeorgia Sotiropoulou

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