Sodium selenate mitigates tau pathology, neurodegeneration, and functional deficits in Alzheimer's disease models.

Proceedings of the National Academy of Sciences of the United States of America
Janet van EerselLars M Ittner

Abstract

Alzheimer's disease (AD) brains are characterized by amyloid-beta-containing plaques and hyperphosphorylated tau-containing neurofibrillary tangles (NFTs); however, in frontotemporal dementia, the tau pathology manifests in the absence of overt amyloid-beta plaques. Therapeutic strategies so far have primarily been targeting amyloid-beta, although those targeting tau are only slowly beginning to emerge. Here, we identify sodium selenate as a compound that reduces tau phosphorylation both in vitro and in vivo. Importantly, chronic oral treatment of two independent tau transgenic mouse strains with NFT pathology, P301L mutant pR5 and K369I mutant K3 mice, reduces tau hyperphosphorylation and completely abrogates NFT formation. Furthermore, treatment improves contextual memory and motor performance, and prevents neurodegeneration. As hyperphosphorylation of tau precedes NFT formation, the effect of selenate on tau phosphorylation was assessed in more detail, a process regulated by both kinases and phosphatases. A major phosphatase implicated in tau dephosphorylation is the serine/threonine-specific protein phosphatase 2A (PP2A) that is reduced in both levels and activity in the AD brain. We found that selenate stabilizes PP2A-tau ...Continue Reading

References

Oct 1, 1996·Proceedings of the National Academy of Sciences of the United States of America·C M WischikC R Harrington
Aug 30, 2000·Lancet·M P Rayman
Oct 3, 2000·The Journal of Biological Chemistry·J GötzR M Nitsch
Mar 22, 2001·Experimental Neurology·V Vogelsberg-RagagliaV M Lee
Nov 5, 2002·Annual Review of Pharmacology and Toxicology·Dennis J Selkoe, Dale Schenk
Jan 2, 2003·Nutritional Neuroscience·David Benton
Aug 2, 2003·The Journal of Biological Chemistry·Alessandra FerrariJürgen Götz
Nov 19, 2003·Journal of Alzheimer's Disease : JAD·Mar PérezJesús Avila
Mar 10, 2004·Biochemistry·Carmen ChiritaJeff Kuret
Apr 2, 2004·Neurobiology of Disease·Luis PennanenJürgen Götz
Dec 22, 2004·The Journal of Biological Chemistry·Sayuri TaniguchiMasato Hasegawa
Dec 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Bin ZhangJohn Q Trojanowski
Nov 3, 2005·The European Journal of Neuroscience·Fei LiuCheng-Xin Gong
Dec 22, 2005·Human Molecular Genetics·Zdenek BergerDavid C Rubinsztein
Apr 4, 2006·Biochemical and Biophysical Research Communications·Andreas SchildJürgen Götz
Jun 14, 2006·Proceedings of the National Academy of Sciences of the United States of America·Sylvie Le CorreHanno M Roder
Nov 30, 2006·Epidemiology·Tasnime N AkbaralyClaudine Berr
Jan 25, 2007·Nature Reviews. Molecular Cell Biology·Christian Haass, Dennis J Selkoe
Feb 17, 2007·The Journal of Clinical Investigation·Chad A DickeyLeonard Petrucelli
May 23, 2007·Proceedings of the National Academy of Sciences of the United States of America·Wenjie LuoGabriela Chiosis
Aug 9, 2007·Nature Reviews. Neuroscience·Carlo BallatoreJohn Q Trojanowski
Aug 24, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ayodeji A AsuniEinar M Sigurdsson
Jan 18, 2008·The Journal of Pharmacology and Experimental Therapeutics·Yasuji MatsuokaPaul S Aisen
Jun 24, 2008·Nature Reviews. Neuroscience·Jürgen Götz, Lars M Ittner
Oct 4, 2008·Proceedings of the National Academy of Sciences of the United States of America·Lars M IttnerJürgen Götz
Jan 8, 2009·Biochemical and Biophysical Research Communications·Natasha DetersJürgen Götz
Jan 10, 2009·Nature Protocols·Thomas FathLars M Ittner
Jun 6, 2009·The Journal of Biological Chemistry·Lars M IttnerJürgen Götz
Aug 21, 2009·Journal of Neural Transmission·Janet van EerselLars M Ittner
Oct 2, 2009·Nature Reviews. Drug Discovery·Kurt R BrundenVirginia M-Y Lee

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Citations

May 21, 2013·Lancet Neurology·Maria Grazia Spillantini, Michel Goedert
Jan 5, 2011·Nature Reviews. Neuroscience·Lars M Ittner, Jürgen Götz
May 15, 2013·PloS One·Sefika OzcelikDavid Theo Winkler
Jun 8, 2011·Future Medicinal Chemistry·Michael VoronkovJeffry B Stock
Jan 8, 2014·Annual Review of Pharmacology and Toxicology·Karen Chiang, Edward H Koo
Apr 7, 2012·International Journal of Alzheimer's Disease·Siddhartha Mondragón-RodríguezJannic Boehm
Apr 1, 2014·Biological Trace Element Research·Sreeram Krishnan, P Rani
Apr 8, 2014·Evidence-based Complementary and Alternative Medicine : ECAM·Hidetoshi WatariChihiro Tohda
Oct 23, 2012·Journal of Neurology, Neurosurgery, and Psychiatry·Yasumasa YoshiyamaJohn Q Trojanowski
Jul 1, 2014·Biological Trace Element Research·Matthew W PittsMarla J Berry
Jul 11, 2013·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Irena MusikJoanna Kocot
Jun 11, 2014·International Journal of Molecular Sciences·Xiubo DuQiong Liu
Jan 23, 2016·Journal of Molecular Neuroscience : MN·Marzieh Dehghan-ShasaltanehGholam Hossein Riazi
Mar 20, 2014·Science China. Life Sciences·Jing LuJürgen Götz
Feb 18, 2016·Neural Plasticity·Jaume FolchAntoni Camins
Jul 16, 2013·Redox Report : Communications in Free Radical Research·Greg T SutherlandPaul K Witting
Sep 14, 2015·Molecular Neurobiology·Cheng-Cheng ZhangJin-Tai Yu
Mar 17, 2015·Brain : a Journal of Neurology·Sandy R ShultzTerence J O'Brien
May 6, 2015·Nature Reviews. Neurology·Lars M IttnerMatthew C Kiernan
Sep 18, 2012·Ageing Research Reviews·Chaoyun LiHermann Schluesener
Mar 22, 2014·Frontiers in Molecular Neuroscience·Jean-Marie Sontag, Estelle Sontag
Jun 19, 2013·Experimental Cell Research·Takanori TsukamotoHiroyuki Tsuchiya
Aug 18, 2016·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Jan AasethUrban Alehagen
Dec 3, 2014·Neurobiology of Aging·Tariq AhmedDetlef Balschun
Oct 14, 2016·PloS One·Annika van HummelLars M Ittner
Nov 28, 2014·Neuropathology and Applied Neurobiology·S DujardinL Buée
May 8, 2014·Metallomics : Integrated Biometal Science·Claire M WeekleyHugh H Harris
Jan 16, 2017·Neuroscience and Biobehavioral Reviews·Rebekah M AhmedLars M Ittner

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