NOTE: It was recently brought to our attention that certain individuals are trying to sell on the internet a nutritional approach to inhibit STEP activity. This nutritional approach is claimed to have "cured" the cognitive deficits in treated Alzheimer's patients. They cite our recent paper on TC-2153 and the finding that it reverses cognitive deficits in a mouse model of Alzheimer's disease. Anyone who sees this advertisement is strongly advised to question its validity, as the only experiments we have conducted to date have been on mice. There is no validity to claims that TC-2153 works in humans nor that the treatment proposed in the advertisement has any relationship to TC-2153 or to our research.

Selected STEP Publications


Synthesis of benzopentathiepin analogs and their evaluation as inhibitors of the phosphatase STEP.

Baguley TD, Nairn AC, Lombroso PJ, Ellman JA.

Bioorg Med Chem Lett. 2015 Mar 1;25 (5) :1044-6. Epub 2015 Jan 20. PMID: 25666825


STEP61 is a substrate of the E3 ligase parkin and is upregulated in Parkinson's disease.

Kurup PK, Xu J, Videira RA, Ononenyi C, Baltazar G, Lombroso PJ, Nairn AC.

Proc Natl Acad Sci U S A. 2015 Jan 27;112 (4) :1202-7. Epub 2015 Jan 12. PMID: 25583483


Disruption of striatal-enriched protein tyrosine phosphatase (STEP) function in neuropsychiatric disorders.

Karasawa T, Lombroso PJ.

Neurosci Res. 2014 Dec;89 :1-9. Epub 2014 Sep 10. PMID: 25218562


Inhibitor of the tyrosine phosphatase STEP reverses cognitive deficits in a mouse model of Alzheimer's disease.

Xu J, Chatterjee M, Baguley TD, Brouillette J, Kurup P, Ghosh D, Kanyo J, Zhang Y, Seyb K, Ononenyi C, Foscue E, Anderson GM, Gresack J, Cuny GD, Glicksman MA, Greengard P, Lam TT, Tautz L, Nairn AC, Ellman JA, Lombroso PJ.

PLoS Biol. 2014 Aug;12 (8) :e1001923. Epub 2014 Aug 5. PMID: 25093460


Cocaine-induced changes of synaptic transmission in the striatum are modulated by adenosine A2A receptors and involve the tyrosine phosphatase STEP.

Chiodi V, Mallozzi C, Ferrante A, Chen JF, Lombroso PJ, Di Stasi AM, Popoli P, Domenici MR.

Neuropsychopharmacology. 2014 Feb;39 (3) :569-78. Epub 2013 Aug 30. PMID: 23989619


Neuroprotective role of a brain-enriched tyrosine phosphatase, STEP, in focal cerebral ischemia.

Deb I, Manhas N, Poddar R, Rajagopal S, Allan AM, Lombroso PJ, Rosenberg GA, Candelario-Jalil E, Paul S.

J Neurosci. 2013 Nov 6;33 (45) :17814-26. PMID: 24198371


Substrate-based fragment identification for the development of selective, nonpeptidic inhibitors of striatal-enriched protein tyrosine phosphatase.

Baguley TD, Xu HC, Chatterjee M, Nairn AC, Lombroso PJ, Ellman JA.

J Med Chem. 2013 Oct 10;56 (19) :7636-50. Epub 2013 Oct 1. PMID: 24083656


A common STEP in the synaptic pathology of diverse neuropsychiatric disorders.

Johnson MA, Lombroso PJ.

Yale J Biol Med. 2012 Dec;85 (4) :481-90. Epub 2012 Dec 13. PMID: 23239949


Striatal-enriched protein-tyrosine phosphatase (STEP) regulates Pyk2 kinase activity.

Xu J, Kurup P, Bartos JA, Patriarchi T, Hell JW, Lombroso PJ.

J Biol Chem. 2012 Jun 15;287 (25) :20942-56. Epub 2012 Apr 27. PMID: 22544749


Striatal-enriched protein tyrosine phosphatase in Alzheimer's disease.

Xu J, Kurup P, Nairn AC, Lombroso PJ.

Adv Pharmacol. 2012;64 :303-25. PMID: 22840751


Therapeutic implications for striatal-enriched protein tyrosine phosphatase (STEP) in neuropsychiatric disorders.

Goebel-Goody SM, Baum M, Paspalas CD, Fernandez SM, Carty NC, Kurup P, Lombroso PJ.

Pharmacol Rev. 2012 Jan;64 (1) :65-87. Epub 2011 Nov 16. PMID: 22090472


Taking STEPs forward to understand fragile X syndrome.

Goebel-Goody SM, Lombroso PJ.

Results Probl Cell Differ. 2012;54 :223-41. PMID: 22009355


Reduced levels of the tyrosine phosphatase STEP block β amyloid-mediated GluA1/GluA2 receptor internalization.

Zhang Y, Kurup P, Xu J, Anderson GM, Greengard P, Nairn AC, Lombroso PJ.

J Neurochem. 2011 Nov;119 (3) :664-72. Epub 2011 Sep 21. PMID: 21883219


Striatal-enriched protein tyrosine phosphatase (STEP) knockout mice have enhanced hippocampal memory.

Venkitaramani DV, Moura PJ, Picciotto MR, Lombroso PJ.

Eur J Neurosci. 2011 Jun;33 (12) :2288-98. Epub 2011 Apr 19. PMID: 21501258


Genetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular deficits in an Alzheimer's disease mouse model.

Zhang Y, Kurup P, Xu J, Carty N, Fernandez SM, Nygaard HB, Pittenger C, Greengard P, Strittmatter SM, Nairn AC, Lombroso PJ.

Proc Natl Acad Sci U S A. 2010 Nov 2;107 (44) :19014-9. Epub 2010 Oct 18. PMID: 20956308


The role of STEP in Alzheimer's disease.

Kurup P, Zhang Y, Venkitaramani DV, Xu J, Lombroso PJ.

Channels (Austin). 2010 Sep-Oct;4 (5) :347-50. Epub 2010 Sep 6. PMID: 20699650


Abeta-mediated NMDA receptor endocytosis in Alzheimer's disease involves ubiquitination of the tyrosine phosphatase STEP61.

Kurup P, Zhang Y, Xu J, Venkitaramani DV, Haroutunian V, Greengard P, Nairn AC, Lombroso PJ.

J Neurosci. 2010 Apr 28;30 (17) :5948-57. PMID: 20427654


Extrasynaptic NMDA receptors couple preferentially to excitotoxicity via calpain-mediated cleavage of STEP.

Xu J, Kurup P, Zhang Y, Goebel-Goody SM, Wu PH, Hawasli AH, Baum ML, Bibb JA, Lombroso PJ.

J Neurosci. 2009 Jul 22;29 (29) :9330-43. PMID: 19625523


A substrate trapping mutant form of striatal-enriched protein tyrosine phosphatase prevents amphetamine-induced stereotypies and long-term potentiation in the striatum.

Tashev R, Moura PJ, Venkitaramani DV, Prosperetti C, Centonze D, Paul S, Lombroso PJ.

Biol Psychiatry. 2009 Apr 15;65 (8) :637-45. Epub 2008 Nov 20. PMID: 19026408


Knockout of striatal enriched protein tyrosine phosphatase in mice results in increased ERK1/2 phosphorylation.

Venkitaramani DV, Paul S, Zhang Y, Kurup P, Ding L, Tressler L, Allen M, Sacca R, Picciotto MR, Lombroso PJ.

Synapse. 2009 Jan;63 (1) :69-81. PMID: 18932218


The tyrosine phosphatase STEP mediates AMPA receptor endocytosis after metabotropic glutamate receptor stimulation.

Zhang Y, Venkitaramani DV, Gladding CM, Zhang Y, Kurup P, Molnar E, Collingridge GL, Lombroso PJ.

J Neurosci. 2008 Oct 15;28 (42) :10561-6. PMID: 18923032


Translation of striatal-enriched protein tyrosine phosphatase (STEP) after beta1-adrenergic receptor stimulation.

Hu Y, Zhang Y, Venkitaramani DV, Lombroso PJ.

J Neurochem. 2007 Oct;103 (2) :531-41. Epub 2007 Jul 10. PMID: 17623046


The striatal-enriched protein tyrosine phosphatase gates long-term potentiation and fear memory in the lateral amygdala.

Paul S, Olausson P, Venkitaramani DV, Ruchkina I, Moran TD, Tronson N, Mills E, Hakim S, Salter MW, Taylor JR, Lombroso PJ.

Biol Psychiatry. 2007 May 1;61 (9) :1049-61. Epub 2006 Nov 1. PMID: 17081505


NMDA-mediated activation of the tyrosine phosphatase STEP regulates the duration of ERK signaling.

Paul S, Nairn AC, Wang P, Lombroso PJ.

Nat Neurosci. 2003 Jan;6 (1) :34-42. PMID: 12483215


Striatal enriched phosphatase 61 dephosphorylates Fyn at phosphotyrosine 420.

Nguyen TH, Liu J, Lombroso PJ.

J Biol Chem. 2002 Jul 5;277 (27) :24274-9. Epub 2002 Apr 30. PMID: 11983687