Alzheimer's & Dementia: The Journal of the Alzheimer's Association
Volume 4, Issue 2 , Pages 89-93 , March 2008

New directions for frontotemporal dementia drug discovery

  • John Q. Trojanowski

      Affiliations

    • Institute on Aging, Center for Neurodegenerative Disease Research, and Department of Pathology and Laboratory, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    • Corresponding Author InformationCorresponding author. Tel.: 215-662-6399; Fax: 215-349-5909.
    • ,
  • Karen Duff

      Affiliations

    • Department of Pathology, Columbia University College of Physicians and Surgeons, New York, NY, USA
    • ,
  • Howard Fillit

      Affiliations

    • Institute for the Study of Aging, New York, NY, USA
    • ,
  • Walter Koroshetz

      Affiliations

    • National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
    • ,
  • Jeff Kuret

      Affiliations

    • The Ohio State University, Columbus, OH, USA
    • ,
  • Diane Murphy

      Affiliations

    • National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
    • ,
  • Larry Refolo

      Affiliations

    • National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA

References 

  1. Skovronsky DM, Lee VM-Y, Trojanowski JQ. Neurodegenerative diseases: new concepts of pathogenesis and their therapeutic implications. Annu Rev Pathol Mech Dis. 2006;1:151–170
  2. Cairns NJ, Bigio EH, Mackenzie IRA, Neumann M, Lee VM-Y, Hatanpaa KJ, et al. Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: Consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropath. 2007;114:5–22
  3. Kwong K, Neuman M, Samapathu D, Lee VM-Y, Trojanowski JQ. TDP-43 proteinopathy (the neuropathology underlying major forms of sporadic and hereditary frontotemporal lobar degeneration and motor neuron disease). Acta Neuropath. 2007;114:63–70
  4. Neumann M, Sampathu DM, Kwong LK, Traux A, Miscenyi M, Chou TT, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science. 2006;314:130–133
  5. Churcher I. Tau therapeutic strategies for the treatment of Alzheimer’s disease. Curr Top Med Chem. 2006;6:579–595
  6. Fillit HM, Refolo LM. Advancing drug discovery for Alzheimer’s disease. Curr Alzheimer Res. 2005;2:105–109
  7. Lee VM-Y, Trojanowski JQ. Progress from Alzheimer’s tangles to pathological tau points towards more effective therapies now. J Alzheimer’s Disease. 2006;9(suppl):257–262
  8. Roder HM, Hutton ML. Microtubule-associated protein tau as a therapeutic target in neurodegenerative disease. Expert Opin Ther Targets. 2007;11:435–442
  9. Bhat RV, Budd Haeberlein SL, Avila J. Glycogen synthase kinase 3: a drug target for CNS therapies. J Neurochem. 2004;89:1313–1317
  10. Engel T, Goni-Oliver P, Lucas JJ, Avila J, Hernandez F. Chronic lithium administration to FTDP-17 tau and GSK-3beta overexpressing mice prevents tau hyperphosphorylation and neurofibrillary tangle formation, but pre-formed neurofibrillary tangles do not revert. J Neurochem. 2006;99:1445–1455
  11. Noble W, Planel E, Zehr C, Olm V, Meyerson J, Suleman F, et al. Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo. Proc Natl Acad Sci U S A. 2005;102:6990–6995
  12. Ahn JS, Radhakrishnan ML, Mapelli M, Choi S, Tidor B, Cuny GD, et al. Defining Cdk5 ligand chemical space with small molecule inhibitors of tau phosphorylation. Chem Biol. 2005;12:811–823
  13. Le Corre S, Klafki HW, Plesnila N, Hubinger G, Obermeier A, Sahagun H, et al. An inhibitor of tau hyperphosphorylation prevents severe motor impairments in tau transgenic mice. Proc Natl Acad Sci U S A. 2006;103:9673–9678
  14. Dickey CA, Dunmore J, Lu B, Wang J, Lee WC, Kamal A, et al. HSP induction mediates selective clearance of tau phosphyorylated at praline-directed Ser/Thr sites but not KXGS (MARK) sites. FASEB J. 2006;6:753–755
  15. Dickey CA, Eriksen J, Kamal A, Burrows F, Kasibhatla S, Eckman CB, et al. Development of a high throughput drug screening assay for the detection of changes in tau levels: proof of concept with HSP90 inhibitors. Curr Alzheimer Res. 2005;2:231–239
  16. Kuret J, Congdon EE, Li G, Yin H, Yu X, Zhong Q. Evaluating triggers and enhancers of tau fibrillization. Microsc Res Tech. 2005;67:141–155
  17. Pickhardt M, Gazova Z, von Bergen M, Khlistunova I, Wang Y, Hascher A, et al. Anthraquinones inhibit tau aggregation and dissolve Alzheimer’s paired helical filaments in vitro and in cells. J Biol Chem. 2005;280:3628–3635
  18. Zhang B, Maiti A, Shively S, Lakhani F, McDonald-Jones G, Bruce J, et al. Microtubule binding drugs offset tau sequestration by stabilizing microtubules and reversing fast axonal transport deficits in a murine neurodegenerative tauopathy model. Proc Natl Acad Sci U S A. 2006;102:227–231
  19. Yoshiyama Y, Higuchi M, Zhang B, Huang S-M, Iwata N, Saido TC, et al. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron. 2007;53:337–351

PII: S1552-5260(07)00548-1

doi: 10.1016/j.jalz.2007.06.001

Alzheimer's & Dementia: The Journal of the Alzheimer's Association
Volume 4, Issue 2 , Pages 89-93 , March 2008

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