Ottavio Arancio, MD, PhD

Departments And Divisions

  • Department of Pathology & Cell Biology
  • Associate Professor of Pathology and Cell Biology (in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain)
Ottavio Arancio, <span>MD, PhD</span>

Research in my laboratory stems from my life-long commitment to studying mechanisms of synaptic plasticity. I am interested in the cellular and molecular mechanisms that underlie long-lasting changes of synaptic function in both normal, healthy brains and in the brains of those affected by neurological disorders, in particular Alzheimer's disease (AD). Research in my laboratory focuses on the mechanisms by which oligoemric proteins including amyloid-β (Aβ) peptides and tau interfere with both memory formation and the regulation of hippocampal long-term potentiation (LTP), an activity-dependent model of synaptic plasticity that is thought to be related with learning and memory. I am interested in how regulation of gene activation and silencing, post-translational mechanisms, channel opening, intracellular calcium transients and changes in transmitter release machinery might participate in basal synaptic transmission and in synaptic plasticity.

    Education & Training

  • MD, PhD, Medicine, University of Pisa (Italy)

Lab Locations

  • 630 West 168th Street
    P&S 12-420D
    New York, NY 10032
    Phone:
    (212) 342-0533
    Fax:
    (212) 305-5498
    Email:
    oa1@cumc.columbia.edu

Patents

a) Methods and Compositions for Enhancing Memory. The invention is directed to methods for enhancing memory by administering low doses of beta amyloid peptide. The invention also encompasses methods for increasing synaptic plasticity in a subject which comprises administering to the subject low doses of beta amyloid peptide.

Filed on 03/30/09, Patent application number: 12/414160

Inventors: Arancio, O., Puzzo, D., Alberini, C., Mathews, P

b) Histone acetyltransferase activators and uses thereof. The researchers synthesized a new class of small molecule HAT activators with greater solubility and membrane permeability. The HAT activators work by promoting histone acetylation, as opposed to current therapies aimed at preventing deacetylation with HDAC inhibitors. In vivo studies showed that the compound not only crossed the blood-brain barrier, but also increased histone acetylation levels in the hippocampus and ameliorated memory deficits in a mouse model of Alzheimer's disease.

Filed on 12/10/10, Patent application number: PCT/US2010/059925

Inventors: Arancio, O., Francis Y, Fa' M., Feng Y, Landry, DW, Deng, SX

c) Histone acetyltransferase modulators and uses thereof. The researchers synthesized new small molecules that differentially increase or decrease the HATs, CBP and P300.

Filed on 12/22/11, Patent application number: PCT/US2011/066851

Inventors: Arancio, O., Francis Y, Fa' M., Feng Y, Landry, DW, Fiorito J., Luzac M., Deng, SX

d) Uses of Histone Acetyltransferase activators. The researchers have demonstrated that small molecule HAT activators can be beneficial for cancer treatment.

Filed on 06/11/12, Patent application number: PCT/US2012/041907

Inventors: Arancio, O., Francis Y.

e) Phosphodiesterase inhibitors and uses thereof. The researcher have synthesized a new class of small molecule PDE5 inhibitors for therapeutic use in Alzheimer’s Disease.

Filed on 09/29/09, Patent application number: PCT/US2009/058813

Inventors: Arancio, O., Landry, DW, Feng, Y., Deng, SX

f) Phosphodiesterase inhibitors and uses thereof. The invention provides novel benzonaphthyridine derivatives that inhibit PDE5 for therapeutic use in Alzheimer’s Disease.

Filed on 01/17/13, Patent application number: PCT/US2013/021918

Inventors: Arancio, O., Landry, DW, Fiorito, J., Deng, SX, Wasmuth, A.

g) Novel Phosphodiesterase inhibitors and uses thereof. The invention provides novel benzonaphthyridine derivatives that inhibit PDE5 for therapeutic use in Alzheimer’s Disease.

Provisional 0019240.00963US3

Inventors: Arancio, O., Landry, DW, Fiorito, J., Deng, SX, Wasmuth, A.

h) Increasing learning and memory in amyloid-β related neurodegenerative disorders such as Alzheimer's.  The invention is directed to methods for increasing learning and memory in a subject with a neuropathological condition, specifically a condition related to elevated beta-amyloid deposition, the method comprising administering to the subject an effective amount of a compound capable of increasing the activity of Uch-L1. The invention is also directed to screening methods for identifying compounds that enhance

the activity of the proteasome system, Uch-L1, or both.

Filing date: Jun 29, 2006 Issued patent: US7947279 (Issue date May 24, 2011)

Inventors: Arancio, O. Shelanski, M.L., Gong, B.

i) New compounds having a selective PDE4D inhibiting activity. The invention is directed towards the synthesis of a new class of phosphodiesterase 4D inhibitors for the therapy of Alzheimer’s disease

Filing date: 14/02/14. Patent application number: 14425015.6

Inventors: Arancio, O., Fa’, M., Prickaerts, J., Bruno, O., Fossa, P., Fedele, E., Ricciarelli, R.

l) Novel cysteine protease inhibitors and uses thereof. The invention is directed towards the synthesis of a new class of calpain inhibitors for the therapy of Alzheimer’s disease

Filing date: 02/01/13. Patent application number: PCT/US2013/024364

Inventors: Arancio, O., Fa’, M., Schiefer, I.T., Thatcher, G.R.

m) MAP Kinase modulators and uses thereof. The invention is directed towards the synthesis of a new class of p38alpah MAP kinase inhibitors against neurodegeneration,

Filing date: 03/17/14. Patent application number: PCT/US2014/030260

Inventors: Arancio, O., Watterson, D.M., Pelletier, J.C., Roy, S.M.

Committees/Societies/Memberships

Societies:

                       Society for Neuroscience (USA)

Committes:

1995-2000                   New Zealand Neurological Foundation, Scientific Advisory Board (reviewed grant applications in the field of Neuroscience from Academic Institutions in New Zealand)

2000 - Present Italian Ministry of University, National Scientific Committee for Grant Evaluation (reviewed research projects as an external member of a national panel. Applications are in the field of Neuroscience and are submitted from Academic Institutions in Italy)

2001 - Present Alzheimer’s Association (reviewed international applications submitted to their annual research grants program)

2000 - Present Institute for the Study of Aging / Alzheimer’s Drug Discovery Foundation (member of their Scientific Review Board. Periodically reviewed international grant applications from Academia and Industry. Focus on drug discovery in aging and Alzheimer’s Disease)

2002                            Philip Morris (reviewed grant applications in the field of neuroscience)

2002                “Ad hoc” expert EFSA GMO panel (to advise European Food Safety Authority which is responsible for evaluating the safety of all genetically modified foods).

2003 - Present NIH: served on the following drug discovery review groups (ZRG1 MDCN-C/MNPS-C, ZRG1 GGG-T), as well as review groups for P01s, and special emphasis panels

2004 - Present Wellcome Trust (reviewed grant applications. The Wellcome Trust is the largest charity in the UK funding innovative biomedical research, in the UK and internationally)

2004-2008                   Human Frontier Science Program (reviewed grant applications for Post-Doctoral fellowships. The organization supports novel, innovative and interdisciplinary basic research focused on the complex mechanisms of living organisms.  A clear emphasis is placed on novel collaborations that bring biologists together with scientists from fields such as physics, mathematics, chemistry, computer science and engineering to focus on problems at the frontier of the life sciences).

2006 - Present Science Foundation Ireland (reviewed for the Principal Investigator Programme Grant. The foundation was created by the Irish Government to invest significant funds in leading researchers working in fields of science and enginnering)

2007 - Present Medical Research Council (MRC) (reviewed grant applications for the New Investigator Awards. The MRC is funded by the UK Government and supports medical research in the UK)

2008 - Present National Medical Research Council (NMRC) (evaluated applications for Individual Research Grant. The NMRC is funded by the Government of Singapore and supports medical research in Singapore)

2008 - Present Alzheimer’s Society – UK (reviewed applications submitted to their annual research grants program)

2008 - 2012     Department of Veteran Affairs (served on the following review group: Neurobiology D)

2011 - Present Ministero della Salute (Italy) (evaluated applications for Individual Research Grant, Program Projects and Industry/Academia collaborations)

2011                European Research council (evaluated applications for Individual Research Grant)

2012 - Present Research Grant Council (RGC) of Hong Kong (evaluated applications for Individual Research Grant)

2012                Czech Scienze foundation (evaluated applications for Individual Research Grant)

                        2013                NSF (evaluated applications for Individual Research Grant)

2013 - Present The French National Research Agency (ANR) (evaluated applications for Individual Research Grant)

2013 - Present The Netherlands Organisation for Health Research and Development (evaluated applications for Individual Research Grant)

2013 - Present The W. Garfield Weston Foundation (evaluated applications for Individual Research Grant)

2014-2017       Society for Neuroscience Program Committee

Honors & Awards

1987                G. Moruzzi Fellowship, Fidia Research Foundation, Washington, D.C., USA

1990                Anna Villa Rusconi Foundation Prize, Varese, Italy

1990                Fellowship, Fidia SPA, Abano Terme, Italy

1991                            Fellowship, Fidia SPA, Abano Terme, Italy

1991                INSERM Poste vert Fellowship, Paris, France

1994                Fellowship, University of Bologna, Bologna, Italy

2001-2003       Whitehead Fellowship

2001-2004       Speaker’s Fund for Biomedical Research

2004-2006       Investigator Initiated Research Award

2007                AHAF, Centennial Award

2007                Alzheimer’s Association, Zenith Award

2008                Margaret Cahn Research Award

2010                Edward N. and Della L. Thome Memorial Foundation, Award

Research Interests

  • Synapses and Circuits
  • Biophysics/Ion Channels
  • Neural Degeneration and Repair
  • Neurobiology of Learning and Memory
  • Neurobiology of Disease

Publications

Koppensteiner P, Trinchese F, Fà M, Puzzo D, Gulisano W, Yan S, Poussin A, Liu S, Orozco I, Dale E, Teich AF, Palmeri A, Ninan I, Boehm S, Arancio O. Time-dependent reversal of synaptic plasticity induced by physiological concentrations of oligomeric Aβ42: an early index of Alzheimer's disease. Sci Rep. 2016 6:32553. PMCID: PMC5007504

Brullo C, Ricciarelli R, Prickaerts J, Arancio O, Massa M, Rotolo C, Romussi A, Rebosio C, Marengo B, Pronzato MA, van Hagen BT, van Goethem NP, D'Ursi P, Orro A, Milanesi L, Guariento S, Cichero E, Fossa P, Fedele E, Bruno O. New insights into selective PDE4D inhibitors: 3-(Cyclopentyloxy)-4-methoxybenzaldehyde O-(2-(2,6-dimethylmorpholino)-2-oxoethyl) oxime (GEBR-7b) structural development and promising activities to restore memory impairment. Eur J Med Chem. 2016 124:82-102. PMID: 27560284

Manassero G, Guglielmotto M, Zamfir R, Borghi R, Colombo L, Salmona M, Perry G, Odetti P, Arancio O, Tamagno E, Tabaton M. Beta-amyloid 1-42 monomers, but not oligomers, produce PHF-like conformation of Tau protein. Aging Cell. 2016 15:914-23. PMCID: PMC5013016

Luo J, Lee SH, VandeVrede L, Qin Z, Ben Aissa M, Larson J, Teich AF, Arancio O, D'Souza Y, Elharram A, Koster K, Tai LM, LaDu MJ, Bennett BM, Thatcher GR. A multifunctional therapeutic approach to disease modification in multiple familial mouse models and a novel sporadic model of Alzheimer's disease. Mol Neurodegener. 2016 11:35, PMCID: PMC4850651

Teich AF, Sakurai M, Patel M, Holman C, Saeed F, Fiorito J, Arancio O. PDE5 exists in Human Neurons and is a Viable Therapeutic Target for Neurologic Disease. J Alzheimers Dis., 2106  Mar 9. [Epub ahead of print] PMID: 26967220.

Nicholls, R.E., Sontag, J-M., Zhang, H., Staniszewski, A., Yan, S., Kim, C.Y., Yim, M., Woodruff, C.M., Arning, E., Wasek, B., Yin, D., Bottiglieri, T., Sontag, E., Kandel, E.R., Arancio, O., PP2A methylation controls sensitivity and resistance to β-amyloid–induced cognitive and electrophysiological impairments. Proc. Natl. Acad. Sci. U S A, 2016 113:3347-52. PMCID: PMC4812727.

Fá M., Puzzo D., Piacentini R., Staniszewski A., Zhang H., Baltrons M.A., Li Puma D.D., Chatterjee I., Li J., Saeed F., Berman H.L., Ripoli C., Gulisano W., Gonzalez J., Tian H., Costa J.A., Lopez P., Davidowitz E., Yu W.H., Haroutunian V., Brown L.M., Palmeri A., Sigurdsson E.M., Duff K.E., Teich A.F., Honig L.S., Sierks M., Moe J.G., D’Adamio L., Grassi C., Kanaan N.M., Fraser P.E., Arancio O. Extracellular tau oligomers produce an immediate impairment of LTP and memory. Sci Rep. 2016 6: 19393. PMCID: PMC4726138

Luo J, Lee SH, VandeVrede L, Qin Z, Piyankarage S, Tavassoli E, Asghodom RT, Ben Aissa M, Fà M, Arancio O, Yue L, Pepperberg DR, Thatcher GR. Re-engineering a neuroprotective, clinical drug as a procognitive agent with high in vivo potency and with GABAA potentiating activity for use in dementia. BMC Neurosci. 2015 16:67. PMID: 26480871.

Fà M, Zhang H, Staniszewski A, Saeed F, Shen LW, Schiefer IT, Siklos MI, Tapadar S, Litosh VA, Libien J, Petukhov PA, Teich AF, Thatcher GR, Arancio O Novel Selective Calpain 1 Inhibitors as Potential Therapeutics in Alzheimer's Disease. J Alzheimers Dis. 2015 49:707-21. PMID: 26484927.

Hue CD, Cho FS, Cao S, Nicholls RE, Vogel Iii EW, Sibindi C, Arancio O, Bass C', Meaney D, Morrison III B 3rd. Time Course and Size of Blood-Brain Barrier Opening in a Mouse Model of Blast-Induced Traumatic Brain Injury. J Neurotrauma. 2015 Sep 28. [Epub ahead of print]. PMID: 26414212

Fang D, Wang Y, Zhang Z, Du H, Yan S, Sun Q, Zhong C, Wu L, Vangavaragu JR, Yan S, Hu G, Guo L, Rabinowitz M, Glaser E, Arancio O, Sosunov AA, McKhann GM, Chen JX, Yan SS. Increased neuronal PreP activity reduces Aβ accumulation, attenuates neuroinflammation and improves mitochondrial and synaptic function in Alzheimer disease's mouse model. Hum Mol Genet. 2015 24: 5198-210. PMID: 26123488

Matsuzaki S, Lee L, Knock E, Srikumar T, Sakurai M, Hazrati LN, Katayama T, Staniszewski A, Raught B, Arancio O, Fraser PE. SUMO1 Affects Synaptic Function, Spine Density and Memory. Sci Rep. 2015 5: 10730. PMID: 26022678

  • Puzzo D, Gulisano W, Palmeri A, Arancio O. (2015). Rodent models for Alzheimer's disease drug discovery. Expert opinion on drug discovery. 10:703-711.

  • Roy SM, Grum-Tokars VL, Schavocky JP, Saeed F, Staniszewski A, et al. (2015). Targeting human central nervous system protein kinases: An isoform selective p38αMAPK inhibitor that attenuates disease progression in Alzheimer's disease mouse models. ACS chemical neuroscience. 6:666-680.
  • Kim S, Titcombe RF, Zhang H, Khatri L, Girma HK, et al. (2015) . Network compensation of cyclic GMP-dependent protein kinase II knockout in the hippocampus by Ca2+-permeable AMPA receptors. Proceedings of the National Academy of Sciences of the United States of America. 112:3122-127.
  • Nestor MW, Jacob S, Sun B, Prè D, Sproul AA, et al. (2015). Characterization of a subpopulation of developing cortical interneurons from human iPSCs within serum-free embryoid bodies. American journal of physiology. Cell physiology. 308:C209-219.
  • Teich AF, Nicholls RE, Puzzo D, Fiorito J, Purgatorio R, et al. (2015). Synaptic therapy in Alzheimer's disease: a CREB-centric approach. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. 12:29-41.
  • Lee L, Dale E, Staniszewski A, Zhang H, Saeed F, et al. (2014). Regulation of synaptic plasticity and cognition by SUMO in normal physiology and Alzheimer's disease. Scientific reports. 4:7190.
  • Koppensteiner P, Boehm S, Arancio O. (2014). Electrophysiological profiles of induced neurons converted directly from adult human fibroblasts indicate incomplete neuronal conversion.
  • Cellular reprogramming. 16:439-446.
  • Guglielmotto M, Monteleone D, Piras A, Valsecchi V, Tropiano M, et al. (2014). Aβ1-42 monomers or oligomers have different effects on autophagy and apoptosis. Autophagy. 10:1827-1843.
  • Yan S, Li Z, Li H, Arancio O, Zhang W. (2014). Notoginsenoside R1 increases neuronal excitability and ameliorates synaptic and memory dysfunction following amyloid elevation.
  • Scientific reports. 4:6352.
  • Tang G, Gudsnuk K, Kuo SH, Cotrina ML, Rosoklija G, et al. (2014). Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits. Neuron. 83:1131-1143.
  • Ren H, Yan S, Zhang B, Lu TY, Arancio O, et al. (2014). Glut4 expression defines an insulin-sensitive hypothalamic neuronal population. Molecular metabolism. 3:452-459.
  • Origlia N, Criscuolo C, Arancio O, Yan SS, Domenici L. (2014). RAGE inhibition in microglia prevents ischemia-dependent synaptic dysfunction in an amyloid-enriched environment.
  • The Journal of neuroscience: the official journal of the Society for Neuroscience. 34:8749-8760.
  • Puzzo D, Lee L, Palmeri A, Calabrese G, Arancio O. (2014). Behavioral assays with mouse models of Alzheimer's disease: practical considerations and guidelines. Biochemical pharmacology. 88:450-467.
  • Ricciarelli R, Puzzo D, Bruno O, Canepa E, Gardella E, et al. (2014). A novel mechanism for cyclic adenosine monophosphate-mediated memory formation: Role of amyloid beta. 
  • Annals of neurology. 75:602-607.
  • Puzzo D, Loreto C, Giunta S, Musumeci G, Frasca G, et al. (2014). Effect of phosphodiesterase-5 inhibition on apoptosis and beta amyloid load in aged mice. Neurobiology of aging. 35:520-531.
  • Prè D, Nestor MW, Sproul AA, Jacob S, Koppensteiner P, et al. (2014). A time course analysis of the electrophysiological properties of neurons differentiated from human induced pluripotent stem cells (iPSCs). PloS one. 9:e103418.
  • Fà M, Staniszewski A, Saeed F, Francis YI, Arancio O. (2014). Dynamin 1 is required for memory formation. PloS one. 9:e91954.
  • Izzo NJ, Staniszewski A, To L, Fa M, Teich AF, et al. (2014). Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers I: Abeta 42 oligomer binding to specific neuronal receptors is displaced by drug candidates that improve cognitive deficits. PloS one. 9:e111898.
  • Izzo NJ, Xu J, Zeng C, Kirk MJ, Mozzoni K, et al. (2014). Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers II: Sigma-2/PGRMC1 receptors mediate Abeta 42 oligomer binding and synaptotoxicity. PloS one. 9:e111899.
  • Lee L, Kosuri P, Arancio O. (2014). Picomolar amyloid-β peptides enhance spontaneous astrocyte calcium transients. Journal of Alzheimer's disease : JAD. 38:49-62. NIHMSID: NIHMS595742.
  • Sproul AA, Jacob S, Pre D, Kim SH, Nestor MW, et al. (2014). Characterization and molecular profiling of PSEN1 familial Alzheimer's disease iPSC-derived neural progenitors. PloS one. 9:e84547.
  • Orozco IJ, Koppensteiner P, Ninan I, Arancio O. (2014). The schizophrenia susceptibility gene DTNBP1 modulates AMPAR synaptic transmission and plasticity in the hippocampus of juvenile DBA/2J mice. Molecular and cellular neurosciences. 58:76-84.
  • Lee L, Sakurai M, Matsuzaki S, Arancio O, Fraser P. (2013). SUMO and Alzheimer's disease.
  • Neuromolecular medicine. 15:720-36.
  • Schiefer IT, Tapadar S, Litosh V, Siklos M, Scism R, et al. (2013). Design, synthesis, and optimization of novel epoxide incorporating peptidomimetics as selective calpain inhibitors.
  • Journal of medicinal chemistry. 56:6054-68.
  • Knowles JK, Simmons DA, Nguyen TV, Vander Griend L, Xie Y, et al. (2013). Small molecule p75NTR ligand prevents cognitive deficits and neurite degeneration in an Alzheimer's mouse model. Neurobiology of aging. 34:2052-2063.
  • Fiorito J, Saeed F, Zhang H, Staniszewski A, Feng Y, et al. (2013). Synthesis of quinoline derivatives: discovery of a potent and selective phosphodiesterase 5 inhibitor for the treatment of Alzheimer's disease. European journal of medicinal chemistry. 60:285-294.
  • Xing L, Salas M, Zhang H, Gittler J, Ludwig T, et al. (2013). Creation and characterization of BAC-transgenic mice with physiological overexpression of epitope-tagged RCAN1 (DSCR1).
  • Mammalian genome : official journal of the International Mammalian Genome Society. 24:30-43.
  • Pozueta J, Lefort R, Ribe EM, Troy CM, Arancio O, et al. (2013). Caspase-2 is required for dendritic spine and behavioural alterations in J20 APP transgenic mice. Nature communications. 4:1939.
  • Lombino F, Biundo F, Tamayev R, Arancio O, D'Adamio L. (2013). An intracellular threonine of amyloid-β precursor protein mediates synaptic plasticity deficits and memory loss. PloS one. 8(2):e57120.
  • Teich AF, Patel M, Arancio O. 2013. A reliable way to detect endogenous murine β-amyloid.
  • PloS one. 8:e55647.
  • Puzzo D, Arancio O. (2013). Amyloid-β peptide: Dr. Jekyll or Mr. Hyde? Journal of Alzheimer's disease : JAD. 33 Suppl 1:S111-20. NIHMSID: NIHMS483269.
  • Watterson DM, Grum-Tokars VL, Roy SM, Schavocky JP, Bradaric BD, et al. (2013). Development of Novel In Vivo Chemical Probes to Address CNS Protein Kinase Involvement in Synaptic Dysfunction. PloS one. 8:e66226.
  • Tamayev R, Akpan N, Arancio O, Troy CM, D'Adamio L. (2012). Caspase-9 mediates synaptic plasticity and memory deficits of Danish dementia knock-in mice: caspase-9 inhibition provides therapeutic protection. Molecular neurodegeneration. 7:60. PubMed
  • McIntire LB, Berman DE, Myaeng J, Staniszewski A, Arancio O, et al. (2012). Reduction of synaptojanin 1 ameliorates synaptic and behavioral impairments in a mouse model of Alzheimer's disease. The Journal of neuroscience: the official journal of the Society for Neuroscience. 32:15271-6.
  • Teich AF, Arancio O. (2012). Is the amyloid hypothesis of Alzheimer's disease therapeutically relevant? The Biochemical journal. 446:165-177.
  • Liu X, Betzenhauser MJ, Reiken S, Meli AC, Xie W, et al.(2012). Role of leaky neuronal ryanodine receptors in stress-induced cognitive dysfunction. Cell. 150:1055-1067. NIHMSID: NIHMS402231.
  • Qin Z, Luo J, VandeVrede L, Tavassoli E, Fa' M, et al. (2012). Design and synthesis of neuroprotective methylthiazoles and modification as NO-chimeras for neurodegenerative therapy. Journal of medicinal chemistry. 55:6784-6801.
  • Ren H, Orozco IJ, Su Y, Suyama S, Gutiérrez-Juárez R, et al. (2012). FoxO1 target Gpr17 activates AgRP neurons to regulate food intake. Cell. 149:1314-1326.
  • Gaisler-Salomon I, Wang Y, Chuhma N, Zhang H, Golumbic YN, et al. (2012). Synaptic underpinnings of altered hippocampal function in glutaminase-deficient mice during maturation.
  • Hippocampus. 22:1027-1039.
  • Schiefer IT, VandeVrede L, Fa' M, Arancio O, Thatcher GR. (2012). Furoxans (1,2,5-oxadiazole-N-oxides) as novel NO mimetic neuroprotective and procognitive agents. Journal of medicinal chemistry. 55:3076-3087.
  • Tamayev R, Matsuda S, Arancio O, D'Adamio L. (2012). β- but not γ-secretase proteolysis of APP causes synaptic and memory deficits in a mouse model of dementia. EMBO molecular medicine. 4:171-179.
  • Hashimoto G, Sakurai M, Teich AF, Saeed F, Aziz F, et al. (2012). 5-HT₄ receptor stimulation leads to soluble AβPPα production through MMP-9 upregulation. Journal of Alzheimer's disease :JAD. 32:437-445.
  • Duffy AM, Schaner MJ, Wu SH, Staniszewski A, Kumar A, et al. (2011). A selective role for ARMS/Kidins220 scaffold protein in spatial memory and trophic support of entorhinal and frontal cortical neurons. Experimental neurology. 229:409-420.
  • Tamayev R, Matsuda S, Giliberto L, Arancio O, D'Adamio L. (2011). APP heterozygosity averts memory deficit in knockin mice expressing the Danish dementia BRI2 mutant. The EMBO Journal. 30:2501-2509.
  • Puzzo D, Privitera L, Fa' M, Staniszewski A, Hashimoto G, et al. (2011). Endogenous amyloid-β is necessary for hippocampal synaptic plasticity and memory. Annals of neurology. 2011; 69:819-30.
  • Yao J, Du H, Yan S, Fang F, Wang C, et al. (2011). Inhibition of amyloid-beta (Abeta) peptide-binding alcohol dehydrogenase-Abeta interaction reduces Abeta accumulation and improves mitochondrial function in a mouse model of Alzheimer's disease. The Journal of neuroscience : the official journal of the Society for Neuroscience. 31:2313-2320.
  • Wu SH, Arévalo JC, Neubrand VE, Zhang H, Arancio O, et al. (2010). The ankyrin repeat-rich membrane spanning (ARMS)/Kidins220 scaffold protein is regulated by activity-dependent calpain proteolysis and modulates synaptic plasticity. The Journal of biological chemistry. 285:40472-40478.
  • Oliveira TG, Chan RB, Tian H, Laredo M, Shui G, et al. (2010). Phospholipase d2 ablation ameliorates Alzheimer's disease-linked synaptic dysfunction and cognitive deficits. The Journal of neuroscience : the official journal of the Society for Neuroscience. 30:16419-16428.
  • Tamayev R, Matsuda S, Fà M, Arancio O, D'Adamio L. (2010). Danish dementia mice suggest that loss of function and not the amyloid cascade causes synaptic plasticity and memory deficits. Proceedings of the National Academy of Sciences of the United States of America.  107:20822-20827.
  • Tamayev R, Giliberto L, Li W, d'Abramo C, Arancio O, et al. (2010). Memory deficits due to familial British dementia BRI2 mutation are caused by loss of BRI2 function rather than amyloidosis. The Journal of neuroscience : the official journal of the Society for Neuroscience.  30:14915-14924.
  • Arévalo JC, Wu SH, Takahashi T, Zhang H, Yu T, et al. (2010). The ARMS/Kidins220 scaffold protein modulates synaptic transmission. Molecular and cellular neurosciences. 45:92-100.
  • Origlia N, Bonadonna C, Rosellini A, Leznik E, Arancio O, et al. (2010). Microglial receptor for advanced glycation end product-dependent signal pathway drives beta-amyloid-induced synaptic depression and long-term depression impairment in entorhinal cortex. The Journal of neuroscience: the official journal of the Society for Neuroscience. 30:11414-11425.
  • Fa M, Orozco IJ, Francis YI, Saeed F, Gong Y, et al. (2010). Preparation of oligomeric beta-amyloid 1-42 and induction of synaptic plasticity impairment on hippocampal slices. Journal of visualized experiments : JoVE. (41) doi: 10.3791/1884.
  • Origlia N, Arancio O, Domenici L, Yan SS. (2009). MAPK, beta-amyloid and synaptic dysfunction: the role of RAGE. Expert review of neurotherapeutics. 9):1635-1645.
  • Smith DL, Pozueta J, Gong B, Arancio O, Shelanski M. (2009). Reversal of long-term dendritic spine alterations in Alzheimer disease models. Proceedings of the National Academy of Sciences of the United States of America. 106:16877-16882.
  • Gaisler-Salomon I, Miller GM, Chuhma N, Lee S, Zhang H, et al. (2009). Glutaminase-deficient mice display hippocampal hypoactivity, insensitivity to pro-psychotic drugs and potentiated latent inhibition: relevance to schizophrenia. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology. 34:2305-2322.
  • Puzzo D, Staniszewski A, Deng SX, Privitera L, Leznik E, et al. (2009). Phosphodiesterase 5 inhibition improves synaptic function, memory, and amyloid-beta load in an Alzheimer's disease mouse model. The Journal of neuroscience: the official journal of the Society for Neuroscience.  29:8075-8086.
  • Basavarajappa BS, Nixon RA, Arancio O. (2009). Endocannabinoid system: emerging role from neurodevelopment to neurodegeneration. Mini reviews in medicinal chemistry. 9:448-462.
  • Vitolo O, Gong B, Cao Z, Ishii H, Jaracz S, et al. (2009). Protection against beta-amyloid induced abnormal synaptic function and cell death by Ginkgolide J. Neurobiology of aging. 30:257-265.
  • Origlia N, Capsoni S, Cattaneo A, Fang F, Arancio O, et al. (2009). Abeta-dependent Inhibition of LTP in different intracortical circuits of the visual cortex: the role of RAGE. Journal of Alzheimer's disease: JAD. 17:59-68.
  • Francis YI, Fà M, Ashraf H, Zhang H, Staniszewski A, et al. (2009). Dysregulation of histone acetylation in the APP/PS1 mouse model of Alzheimer's disease. Journal of Alzheimer's disease: JAD. 18:131-139.
  • Puzzo D, Privitera L, Leznik E, Fà M, Staniszewski A, et al. (2008). Picomolar amyloid-beta positively modulates synaptic plasticity and memory in hippocampus. The Journal of neuroscience : the official journal of the Society for Neuroscience. 28:14537-14545.
  • Basavarajappa BS, Ninan I, Arancio O. (2008). Acute ethanol suppresses glutamatergic neurotransmission through endocannabinoids in hippocampal neurons. Journal of neurochemistry. 107(4):1001-13.
  • Du H, Guo L, Fang F, Chen D, Sosunov AA, et al. (2008). Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nature medicine. 14:1097-105.
  • Trinchese F, Fa' M, Liu S, Zhang H, Hidalgo A, et al. (2008). Inhibition of calpains improves memory and synaptic transmission in a mouse model of Alzheimer disease. The Journal of clinical investigation. 118:2796-807.
  • Arancio O. (2008). PIP2: a new key player in Alzheimer's disease. Cellscience. 5:44-47.
  • Voronov SV, Frere SG, Giovedi S, Pollina EA, Borel C, et al. (2008). Synaptojanin 1-linked phosphoinositide dyshomeostasis and cognitive deficits in mouse models of Down's syndrome.
  • Proceedings of the National Academy of Sciences of the United States of America. 105:9415-20.
  • Serulle Y, Arancio O, Ziff EB. (2008). A role for cGMP-dependent protein kinase II in AMPA receptor trafficking and synaptic plasticity. Channels (Austin, Tex.). 2:230-2.
  • Liu L, Orozco IJ, Planel E, Wen Y, Bretteville A, et al. (2008). A transgenic rat that develops Alzheimer's disease-like amyloid pathology, deficits in synaptic plasticity and cognitive impairment. Neurobiology of disease. 31:46-57.
  • Muhammad A, Flores I, Zhang H, Yu R, Staniszewski A, et al. (2008). Retromer deficiency observed in Alzheimer's disease causes hippocampal dysfunction, neurodegeneration, and Abeta accumulation. Proceedings of the National Academy of Sciences of the United States of America. 105:7327-32.
  • Berman DE, Dall'Armi C, Voronov SV, McIntire LB, Zhang H, et al. (2008). Oligomeric amyloid-beta peptide disrupts phosphatidylinositol-4,5-bisphosphate metabolism. Nature neuroscience. 2008; 11(5):547-54.
  • Puzzo D, Sapienza S, Arancio O, Palmeri A. (2008). Role of phosphodiesterase 5 in synaptic plasticity and memory. Neuropsychiatric disease and treatment. 4:371-87.
  • Matsuoka Y, Jouroukhin Y, Gray AJ, Ma L, Hirata-Fukae C, et al. (2008). A neuronal microtubule-interacting agent, NAPVSIPQ, reduces tau pathology and enhances cognitive function in a mouse model of Alzheimer's disease. The Journal of pharmacology and experimental therapeutics. 325:146-53.
  • Origlia N, Righi M, Capsoni S, Cattaneo A, Fang F, et al. (2008). Receptor for advanced glycation end product-dependent activation of p38 mitogen-activated protein kinase contributes to amyloid-beta-mediated cortical synaptic dysfunction. The Journal of neuroscience : the official journal of the Society for Neuroscience. 28:3521-30.
  • Yang T, Knowles JK, Lu Q, Zhang H, Arancio O, et al.(2008). Small molecule, non-peptide p75 ligands inhibit Abeta-induced neurodegeneration and synaptic impairment. PloS one. 3:e3604.
  • Echeverria V, Berman DE, Arancio O. (2007). Oligomers of beta-amyloid peptide inhibit BDNF-induced arc expression in cultured cortical Neurons. Current Alzheimer research. 4:518-21.
  • Chen X, Walker DG, Schmidt AM, Arancio O, Lue LF, et al. (2007). RAGE: a potential target for Abeta-mediated cellular perturbation in Alzheimer's disease. Current molecular medicine. 7:735-42.
  • Serulle Y, Zhang S, Ninan I, Puzzo D, McCarthy M, et al. (2007). A GluR1-cGKII interaction regulates AMPA receptor trafficking. Neuron. 56:670-88.
  • Arancio O, Chao MV. (2007). Neurotrophins, synaptic plasticity and dementia. Current opinion in neurobiology. 17:325-30.
  • Liu S, Fa M, Ninan I, Trinchese F, Dauer W, et al. (2007). Alpha-synuclein involvement in hippocampal synaptic plasticity: role of NO, cGMP, cGK and CaMKII. The European journal of neuroscience. 25:3583-96.
  • Ninan I, Liu S, Rabinowitz D, Arancio O. (2006). Early presynaptic changes during plasticity in cultured hippocampal neurons. The EMBO journal. 25:4361-71.
  • Ninan I, Arancio O, Rabinowitz D. (2006). Estimation of the mean from sums with unknown numbers of summands. Biometrics. 62:918-20.
  • Gong B, Cao Z, Zheng P, Vitolo OV, Liu S, et al. (2006). Ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory. Cell. 126:775-88.
  • Yano H, Ninan I, Zhang H, Milner TA, Arancio O, et al. (2006). BDNF-mediated neurotransmission relies upon a myosin VI motor complex. Nature Neuroscience. 9:1009-18.
  • Puzzo D, Arancio O. (2006). Fibrillar beta-amyloid impairs the late phase of long term potentiation. Current Alzheimer research. 3:179-83.
  • Moretti P, Levenson JM, Battaglia F, Atkinson R, Teague R, et al. (2006). Learning and memory and synaptic plasticity are impaired in a mouse model of Rett syndrome. The Journal of neuroscience : the official journal of the Society for Neuroscience. 26:319-27.
  • Puzzo D, Palmeri A, Arancio O. (2006). Involvement of the nitric oxide pathway in synaptic dysfunction following amyloid elevation in Alzheimer's disease. Reviews in the neurosciences.  17:497-523.
  • Puzzo D, Vitolo O, Trinchese F, Jacob JP, Palmeri A, et al. (2005). Amyloid-beta peptide inhibits activation of the nitric oxide/cGMP/cAMP-responsive element-binding protein pathway during hippocampal synaptic plasticity. The Journal of neuroscience: the official journal of the Society for Neuroscience. 25:6887-97.
  • Takuma K, Yao J, Huang J, Xu H, Chen X, et al. (2005). ABAD enhances Abeta-induced cell stress via mitochondrial dysfunction. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 19:597-8.
  • Zhang H, Gong B, Liu S, Fa' M, Ninan I, et al. (2005). Synaptic fatigue is more pronounced in the APP/PS1 transgenic mouse model of Alzheimer's disease. Current Alzheimer research.  2:137-40.
  • Gong B, Vitolo OV, Trinchese F, Liu S, Shelanski M, et al. (2004). Persistent improvement in synaptic and cognitive functions in an Alzheimer mouse model after rolipram treatment. The Journal of clinical investigation. 114:1624-34.
  • Liu S, Ninan I, Antonova I, Battaglia F, Trinchese F, et al. (2004). alpha-Synuclein produces a long-lasting increase in neurotransmitter release. The EMBO Journal. 23:4506-16.
  • Arancio O, Zhang HP, Chen X, Lin C, Trinchese F, et al. (2004). RAGE potentiates Abeta-induced perturbation of neuronal function in transgenic mice. The EMBO Journal. 23:4096-105.
  • Veeranna, Kaji T, Boland B, Odrljin T, Mohan P, et al. (2004). Calpain mediates calcium-induced activation of the erk1,2 MAPK pathway and cytoskeletal phosphorylation in neurons: relevance to Alzheimer's disease. The American journal of pathology. 165:795-805.
  • Trinchese F, Liu S, Battaglia F, Walter S, Mathews PM, et al. (2004). Progressive age-related development of Alzheimer-like pathology in APP/PS1 mice. Annals of neurology. 55:801-14.
  • Lustbader JW, Cirilli M, Lin C, Xu HW, Takuma K, et al. (2004). ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease. Science (New York, N.Y.) 304:448-52.
  • Ninan I, Arancio O. (2004). Presynaptic CaMKII is necessary for synaptic plasticity in cultured hippocampal neurons. Neuron. 42:129-41.
  • Trinchese F, Liu S, Ninan I, Puzzo D, Jacob JP, et al. (2004). Cell cultures from animal models of Alzheimer's disease as a tool for faster screening and testing of drug efficacy. Journal of molecular neuroscience: MN. 24:15-21.
  • Di Rosa G, Puzzo D, Sant'Angelo A, Trinchese F, Arancio O. (2003). Alpha-synuclein: between synaptic function and dysfunction. Histology and histopathology. 18:1257-66.
  • Petrone A, Battaglia F, Wang C, Dusa A, Su J, et al. (2003). Receptor protein tyrosine phosphatase alpha is essential for hippocampal neuronal migration and long-term potentiation. 
  • The EMBO journal. 22:4121-31.
  • Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, et al. (2003). Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science (New York, N.Y.) 301:805-9.
  • Sant'Angelo A, Trinchese F, Arancio O. (2003). Usefulness of behavioral and electrophysiological studies in transgenic models of Alzheimer's disease. Neurochemical research. 28:1009-15.
  • Battaglia F, Trinchese F, Liu S, Walter S, Nixon RA, et al.(2003). Calpain inhibitors, a treatment for Alzheimer's disease: position paper. Journal of molecular neuroscience : MN. 20:357-62.
  • Vitolo OV, Sant'Angelo A, Costanzo V, Battaglia F, Arancio O, et al. (2002). Amyloid beta -peptide inhibition of the PKA/CREB pathway and long-term potentiation: reversibility by drugs that enhance cAMP signaling. Proceedings of the National Academy of Sciences of the United States of America. 99:13217-21.
  • Di Rosa G, Odrijin T, Nixon RA, Arancio O. (2002). Calpain inhibitors: a treatment for Alzheimer's disease. Journal of molecular neuroscience : MN. 19:135-41.
  • Antonova I, Arancio O, Trillat AC, Wang HG, Zablow L, et al. (2001). Rapid increase in clusters of presynaptic proteins at onset of long-lasting potentiation. Science (New York, N.Y.) 294:1547-50.
  • Arancio O, Antonova I, Gambaryan S, Lohmann SM, Wood JS, et al. (2001). Presynaptic role of cGMP-dependent protein kinase during long-lasting potentiation. The Journal of neuroscience: the official journal of the Society for Neuroscience. 21:143-9.
  • Agnihotri N, López-García JC, Hawkins RD, Arancio O. (1998). Morphological changes associated with long-term potentiation. Histology and histopathology. 13:1155-62.
  • Son H, Lu YF, Zhuo M, Arancio O, Kandel ER, et al. (1998). The specific role of cGMP in hippocampal LTP. Learning & memory (Cold Spring Harbor, N.Y.). 5:231-45.
  • Hawkins RD, Son H, Arancio O. (1998). Nitric oxide as a retrograde messenger during long-term potentiation in hippocampus. Progress in brain research. 118:155-72.
  • Arancio O, Kiebler M, Lee CJ, Lev-Ram V, Tsien RY, et al.(1996). Nitric oxide acts directly in the presynaptic neuron to produce long-term potentiation in cultured hippocampal neurons. Cell.  87:1025-35.
  • Pasino E, Buffelli M, Arancio O, Busetto G, Salviati A, et al. (1996). Effects of long-term conduction block on membrane properties of reinnervated and normally innervated rat skeletal muscle. The Journal of physiology. 497:457-72.
  • López-García JC, Arancio O, Kandel ER, Baranes D. (1996). A presynaptic locus for long-term potentiation of elementary synaptic transmission at mossy fiber synapses in culture. Proceedings of the National Academy of Sciences of the United States of America. 93:4712-7.
  • Arancio O, Lev-Ram V, Tsien RY, Kandel ER, Hawkins RD. (1996). Nitric oxide acts as a retrograde messenger during long-term potentiation in cultured hippocampal neurons. Journal of physiology, Paris. 90:321-2.
  • Arancio O, Kandel ER, Hawkins RD. (1995). Activity-dependent long-term enhancement of transmitter release by presynaptic 3',5'-cyclic GMP in cultured hippocampal neurons. Nature.  376:74-80.
  • Arancio O, Korn H, Gulyas A, Freund T, Miles R. (1995). Excitatory synaptic connections onto rat hippocampal inhibitory cells may involve a single transmitter release site. The Journal of physiology. 481:395-405.
  • Hawkins RD, Zhuo M, Arancio O. (1994). Nitric oxide and carbon monoxide as possible retrograde messengers in hippocampal long-term potentiation. Journal of neurobiology. 25:652-65.
  • Arancio O, Yoshimura M, Murase K, MacDermott AB. (1993). The distribution of excitatory amino acid receptors on acutely dissociated dorsal horn neurons from postnatal rats.
  • Neuroscience. 52:159-67.
  • Arancio O, Buffelli M, Cangiano A, Pasino E. (1992). Nerve stump effects in muscle are independent of synaptic connections and are temporally correlated with nerve degeneration phenomena. Neuroscience letters. 146:1-4.
  • O'Dell TJ, Hawkins RD, Kandel ER, Arancio O. (1991). Tests of the roles of two diffusible substances in long-term potentiation: evidence for nitric oxide as a possible early retrograde messenger. Proceedings of the National Academy of Sciences of the United States of America.  88:11285-9.
  • Yoshimura M, Murase K, Arancio O, MacDermott AB. (1991). Glutamate receptor agonist-induced inward currents in spinal dorsal horn neurons dissociated from the adult rats. Neuroscience research. 12:528-35.
  • Arancio O, MacDermott AB. (1991). Differential distribution of excitatory amino acid receptors on embryonic rat spinal cord neurons in culture. Journal of neurophysiology. 65:899-913.
  • Tiedge H, Fremeau RT Jr, Weinstock PH, Arancio O, Brosius J. (1991). Dendritic location of neural BC1 RNA. Proceedings of the National Academy of Sciences of the United States of America. 88:2093-7.
  • MacDermott AB, Reichling DB, Arancio O. (1990). Mechanisms underlying excitatory amino acid-evoked calcium entry in cultured neurons from the embryonic rat spinal cord.
  • Advances in experimental medicine and biology. 268:117-24.
  • Arancio O, Bonadonna G, Calvani M, Giovene P, Tomelleri G, et al. (1989). Transitory L-carnitine depletion in rat skeletal muscle by D-carnitine. Pharmacological research: the official journal of the Italian Pharmacological Society. 21:163-8.
  • Arancio O, Cangiano A, De Grandis D. (1989). Fibrillatory activity and other membrane changes in partially denervated muscles. Muscle & nerve. 12:149-53.
  • Arancio O, Bongiovanni LG, Bonadonna G, Tomelleri G, De Grandis D. (1988). Congenital muscular dystrophy and cerebellar vermis agenesis in two brothers. Italian journal of neurological sciences. 9:485-9.
  • Provenzano C, Arancio O, Evoli A, Rocca B, Bartoccioni E, et al. (1988). Familial autoimmune myasthenia gravis with different pathogenetic antibodies. Journal of neurology, neurosurgery, and psychiatry. 51:1228-30.
  • Arancio O, Cangiano A, Magherini PC, Pasino E. (1988). Effects of reinnervation with normal and tetrodotoxin-inactive nerves on resting membrane potential of rat skeletal muscle.
  • Neuroscience letters. 88:179-83.
  • De Grandis D, Arancio O, Serra G. (1986). An electroneurographic response. Muscle & nerve.  9:185-6.
  • Polo A, Arancio O, Bronzato P, Serra G, De Grandis D. (1986). Effect of aging on the visual evoked oscillatory potentials in man. [Print]. Riv. Ital. EEG Neurofisiol. Clin.
  • Arancio O, Bongiovanni LG, De Grandis D. (1985). Acute peroneal compartmental syndrome. Report of a case. European neurology. 24:69-72.
  • Arancio O, Cangiano A, Magherini PC. (1982). Role of NGF in the development of primary sensory neurons in the rat. Bollettino della Societa italiana di biologia sperimentale. 58:60-5.

For a complete list of publications, please visit PubMed.gov