The market for neurodegenerative therapeutics.

Signum/Stock Lab

Lee KW, Chen W, Junn E,Grosso H, Im JY, Sonsalla PK, Feng X, Ray N, Fernandez JR, Chao Y, Masliah E, Voronkov M, Braithwaite SP, Stock JB, Mouradian MM (2011) Enhanced phosphatase activity attenuates α-synucleinopathy in a mouse model. J. Neurosci, 31(19):6963-71 PubMed PMID:21562258

Voronkov M, Braithwaite SP, Stock JB (2011) Phosphoprotein Phosphatase 2A: A Novel Drugable Target for Alzheimer's Disease. Future Med Chem 3(7), 821-33 PubMed PMID:21644827

Li Z, Stock JB. Protein carboxyl methylation and the biochemistry of memory. Biol Chem. 2009 Nov;390(11):1087-96. Review. PubMed PMID: 19747079.

Vafai SB, Stock JB. Protein phosphatase 2A methylation: a link between elevated plasma homocysteine and Alzheimer's Disease. FEBS Lett. 2002 May 8;518(1-3):1-4. PubMed PMID: 11997007.

Xing Y, Li Z, Chen Y, Stock JB, Jeffrey PD, Shi Y. Structural mechanism of demethylation and inactivation of protein phosphatase 2A. Cell. 2008 Apr 4;133(1):154-63. PubMed PMID: 18394995.

Stanevich V, Jiang L, Satyshur KA, Li Y, Jeffrey PD, Li Z, Menden P, Semmelhack MF, Xing Y. The Structural Basis for Tight Control of PP2A Methylation and Function by LCMT-1. Mol Cell. 2011 Feb 4;41(3):331-42. PubMed PMID: 21292165.

Tolstykh T, Lee J, Vafai S, Stock JB. Carboxyl methylation regulates phosphoprotein phosphatase 2A by controlling the association of regulatory B subunits. EMBO J. 2000 Nov 1;19(21):5682-91. PubMed PMID: 11060019; PubMed Central PMCID: PMC305779.

Wu J, Tolstykh T, Lee J, Boyd K, Stock JB, Broach JR. Carboxyl methylation of the phosphoprotein phosphatase 2A catalytic subunit promotes its functional association with regulatory subunits in vivo. EMBO J. 2000 Nov 1;19(21):5672-81. PubMed PMID: 11060018; PubMed Central PMCID: PMC305778.

Additional References

Xu Y, Chen Y, Zhang P, Jeffrey PD, Shi Y. Structure of a protein phosphatase 2A holoenzyme: insights into B55-mediated Tau dephosphorylation. Mol Cell. 2008 Sep 26;31(6):873-85. PubMed PMID: 18922469; PubMed Central PMCID: PMC2818795.

Iqbal K, Liu F, Gong CX, Alonso Adel C, Grundke-Iqbal I. Mechanisms of tau-induced neurodegeneration. Acta Neuropathol. 2009 Jul;118(1):53-69. Epub 2009 Jan 30. Review. PubMed PMID: 19184068; PubMed Central PMCID: PMC2872491.

Sontag E, Hladik C, Montgomery L, Luangpirom A, Mudrak I, Ogris E, White CL 3rd. Downregulation of protein phosphatase 2A carboxyl methylation and methyltransferase may contribute to Alzheimer disease pathogenesis. J Neuropathol Exp Neurol. 2004 Oct;63(10):1080-91. PubMed PMID: 15535135.

Sontag E, Luangpirom A, Hladik C, Mudrak I, Ogris E, Speciale S, White CL 3rd. Altered expression levels of the protein phosphatase 2A ABalphaC enzyme are associated with Alzheimer disease pathology. J Neuropathol Exp Neurol. 2004 Apr;63(4):287-301. PubMed PMID: 15099019.

Zhou XW, Gustafsson JA, Tanila H, Bjorkdahl C, Liu R, Winblad B, Pei JJ. Tau hyperphosphorylation correlates with reduced methylation of protein phosphatase 2A. Neurobiol Dis. 2008 Sep;31(3):386-94. Epub 2008 Jul 23. PubMed PMID: 18586097.

Sontag E, Nunbhakdi-Craig V, Sontag JM, Diaz-Arrastia R, Ogris E, Dayal S, Lentz SR, Arning E, Bottiglieri T. Protein phosphatase 2A methyltransferase links homocysteine metabolism with tau and amyloid precursor protein regulation. J Neurosci. 2007 Mar 14;27(11):2751-9. PubMed PMID: 17360897.

Virshup DM, Shenolikar S. From promiscuity to precision: protein phosphatases get a makeover. Mol Cell. 2009 Mar 13;33(5):537-45. Review. PubMed PMID: 19285938.